Spatial control of additives by high temperature

ABSTRACT

Provided is a method of making a polymeric material with a spatially controlled distribution of one or more additives including the steps of blending the one or more additives with a polymeric material, consolidating the polymeric material, heating at least a portion of at least one surface of the consolidated additive-blended polymeric material, and cooling the heated consolidated additive-blended polymeric material, thereby forming a polymeric material with a spatially controlled distribution of additive.

CROSS REFERENCES TO RELATED APPLICATIONS

This application is a divisional application of U.S. patent applicationSer. No. 14/420,005 filed Feb. 6, 2015, which is a 371 application ofPCT/US2013/053396 filed Aug. 2, 2013 which claims priority from U.S.Provisional Patent Application No. 61/679,952, filed Aug. 6, 2012.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

Not Applicable.

BACKGROUND OF THE INVENTION 1. Field of the Invention

The invention describes methods of making cross-linked total jointimplants by controlling the spatial control of anti-cross-linkingagents. The invention uses methods of extracting anti-cross-linkingagents and controlling antioxidant concentrations in polymeric materialsfor joint implants.

2. Background of the Invention

Radiation cross-linking of polymers enhances many of their mechanicalproperties. For ultrahigh molecular weight polyethylene (UHMWPE),radiation cross-linking can also enhance its wear resistance underbi-directional motion similar to that experienced in human joints.However, radiation cross-linking can also decrease the toughness ofUHMWPE with increasing radiation dose. Thus, controlling cross-linkingspatially such that only portions of the polymer are cross-linked may bedesirable to maintain the toughness of the material while improving itswear resistance.

Spatially controlling cross-linking in polymers can be performed inseveral ways; one approach is to use a spatial distribution of anadditive in the polymer which can decrease cross-linking. This inventiondescribes methods of extracting and/or incorporating additives in apolymeric material, for example, to spatially control the concentrationprofile of the additive in the polymeric material.

SUMMARY OF THE INVENTION

Additives can be incorporated into a polymeric material using differentmethods. One method involves blending one or more types of resin, flakesor powder of the polymeric material with different concentrations ofadditives. Then, the polymeric material can be used in unconsolidatedform or consolidated into larger solid forms, for example rectangularblocks or cylindrical pucks from which test coupons, implant preforms,or implants can be machined.

Exposing the consolidated polymeric material containing one or moreadditives (“additives”) to a high temperature may lead to oxidation ofthe polymer, and/or oxidation, consumption, degradation, and/orevaporation of the additives, thereby leading to the extraction of theadditives. Loss of the additives when exposed to high temperature may beon the surface of the material, creating a concentration gradient in thematerial with the bulk having higher concentrations of additives thanthe surface.

One class of additives includes antioxidants. In this case, theadditives can decrease cross-linking in UHMWPE when exposed tocross-linking conditions using radiation or chemical cross-linkingmethods.

In some embodiments, consolidated polymeric material with a spatiallycontrolled distribution of additives is further cross-linked.Cross-linking can be initiated by ionizing radiation such as a gamma orelectron beam irradiation.

A spatially controlled distribution of additives can be created before,during and after extraction of additives from desired surfaces by acombination of diffusion from the bulk and/or diffusion from externalsources. In some embodiments, while extraction is being performed on oneor more desired surfaces by high temperature exposure, an externaldoping source of additive is used from one or more surfaces whereextraction of additive is not desired. The doping source may be used toreplenish some of the additive that has diffused toward the extractedregion on the surface.

If a spatial distribution of additives is not desired during hightemperature melting, then all surfaces of the polymeric need to bemasked to prevent extraction. Alternatively, the surface regions can bemachined away to obtain a medical implant preform or medical implantwith uniform additive concentration or uniform cross-linking afterirradiation.

In any of embodiments, during the high temperature extraction ofadditive from surfaces, implant geometry may change due to thermalprocesses such as melting and recrystallization. In this case, implantpreforms can be used for processing after which one or more machiningsteps can be used to obtain a final solid form intended for use such asan implant.

In one embodiment, the invention provides methods of making polymericmaterial with a spatially controlled distribution of additivecomprising: (a) blending additive with a polymeric material; (b)consolidating the polymeric material; (c) exposing one or moresurface(s) of the consolidated additive-blended polymeric material tohigh temperature; (d) cooling the heated consolidatedantioxidant-blended polymeric material; thereby forming a polymericmaterial with a spatially controlled distribution of additive.

Cooling of any of the polymeric material(s) after high temperatureexposure is performed until the temperature of the polymeric material isbelow the crystallization temperature. Although the final temperature ofthe polymeric material is desired to be close to room temperature (20°C. to 25° C.), cooling can be performed at any rate and any number ofsetpoints below or above room temperature in between. For example, apolymeric material can be cooled by exposing to liquid nitrogen(approximately −196° C.), then warmed to room temperature, or it can bebrought first to 60° C., then cooled to room temperature. The coolingrate can be variable during cooling in a stepwise or in a continuousmanner. Cooling can be done at the same environment as heating or in adifferent environment. Cooling can be performed in inert gas, anon-inert gas, air, vacuum, a liquid, a liquid with gas bubbled through,a liquid saturated with gas, a supercritical fluid or mixtures thereof.Inert gases can be nitrogen or argon or any other inert gas. Cooling canalso be done in direct contact or in a chamber in contact with coolingfluid(s). Such a cooling fluid can be inert gas, water, ethanol, dryice, liquid nitrogen. Heating and/or cooling can be done in static ordynamic flow of fluids in contact with the polymeric material or incontact with the chamber in which the polymeric material is maintained.The duration of cooling finally to room temperature can be between 1minute to 1000 hours, or between 1 hour and 12 hours, more preferablyabout 2 hours.

In one embodiment, the invention provides methods of making polymericmaterial with a spatially controlled distribution of antioxidant(s)comprising: (a) blending antioxidant(s) with a polymeric material; (b)consolidating the polymeric material; (c) exposing one or moresurface(s) of the consolidated antioxidant-blended polymeric material tohigh temperature; (d) cooling the heated consolidatedantioxidant-blended polymeric material; thereby forming a polymericmaterial with a spatially controlled distribution of antioxidant(s).

In one embodiment, the invention provides methods of making polymericmaterial with a spatially controlled distribution of vitamin Ecomprising: (a) blending vitamin E with a polymeric material; (b)consolidating the polymeric material; (c) exposing one or moresurface(s) of the consolidated vitamin E-blended polymeric material tohigh temperature; (d) cooling the heated consolidated vitamin E-blendedpolymeric material; thereby forming a polymeric material with aspatially controlled distribution of vitamin E.

In one embodiment, the invention provides methods of making cross-linkedadditive-blended polymeric material comprising: (a) blending additivewith a polymeric material; (b) consolidating the polymeric material; (c)exposing one or more surface(s) of the consolidated additive-blendedpolymeric material to high temperature; (d) cooling the heatedconsolidated antioxidant-blended polymeric material; (e) irradiating thehigh temperature extracted consolidated additive-blended polymericmaterial thereby forming a cross-linked additive-blended polymericmaterial.

In one embodiment, the invention provides methods of making across-linked antioxidant-blended polymeric material with a spatialdistribution of cross-linking comprising: (a) blending additive with apolymeric material; (b) consolidating the polymeric material; (c)exposing one or more surface(s) of the consolidated additive-blendedpolymeric material to high temperature; (d) cooling the heatedconsolidated antioxidant-blended polymeric material; (e) irradiating thehigh temperature extracted consolidated antioxidant-blended polymericmaterial thereby forming a cross-linked additive-blended polymericmaterial with a spatially controlled distribution of cross-linking.

In one embodiment, the invention provides methods of making across-linked vitamin E-blended polymeric material with a spatialdistribution of cross-linking comprising: (a) blending vitamin E with apolymeric material; (b) consolidating the polymeric material; (c)exposing one or more surface(s) of the consolidated vitamin E-blendedpolymeric material to high temperature; (d) cooling the heatedconsolidated vitamin E-blended polymeric material; (e) irradiating thehigh temperature extracted consolidated vitamin E-blended polymericmaterial thereby forming a cross-linked additive-blended polymericmaterial with a spatially controlled distribution of cross-linking.

In one embodiment, the invention provides methods of making a medicalimplant comprising: (a) blending additive with a polymeric material; (b)consolidating the polymeric material; (c) machining the consolidatedpolymeric material into a medical implant preform; (d) exposing one ormore surface(s) of the medical implant preform to high temperature; (e)cooling the medical implant preform; f) irradiating the medical implantpreform.

In one embodiment, the invention provides methods of making a medicalimplant comprising: (a) blending additive with a polymeric material; (b)consolidating the polymeric material; (c) machining the consolidatedpolymeric material into a medical implant preform; (d) exposing one ormore surface(s) of the medical implant preform to high temperature; (e)cooling the medical implant preform; (f) machining the medical implantpreform, thereby forming a medical implant; and (g) irradiating themedical implant.

In one embodiment, the invention provides methods of making a hybrid,interlocked medical implant comprising: (a) blending additive with apolymeric material; (b) consolidating the polymeric material onto asecond porous material; thereby forming a hybrid, interlocked medicalimplant preform; (c) exposing one or more surface(s) of the hybrid,interlocked medical implant preform to high temperature; (d) cooling thehybrid, interlocked medical implant preform; (e) machining the hybrid,interlocked medical implant preform, thereby forming a medical implant;and (f) irradiating the medical implant.

In one embodiment, the invention provides methods of making a medicalimplant with a spatially controlled distribution of cross-linkingcomprising: (a) blending additive with a polymeric material; (b)consolidating the polymeric material; (c) machining the consolidatedpolymeric material into a medical implant preform; (d) exposing one ormore surface(s) of the medical implant preform to high temperature; (e)cooling the medical implant preform; and (f) irradiating the medicalimplant preform; thereby forming a medical implant with a spatiallycontrolled distribution of cross-linking.

In some embodiments, after high temperature exposure for extraction ofadditive from one or more surface(s), a small amount can be machinedfrom the polymeric material or medical implant preform to obtain a finalmedical implant complying with clearance requirements of a final medicalimplant design. This machining can be 1 micron to 5 millimeters,preferably 100 microns to 1 millimeters, most preferably about 200microns (also micra).

In one embodiment, the invention provides methods of making a medicalimplant with a spatially controlled distribution of cross-linkingcomprising: (a) blending additive with a polymeric material; (b)consolidating the polymeric material; (c) machining the consolidatedpolymeric material into a medical implant preform; (d) exposing one ormore surface(s) of the medical implant preform to high temperature; (e)cooling the medical implant preform; (f) machining the medical implantpreform, thereby forming a medical implant, and (g) irradiating themedical implant; thereby forming a medical implant with a spatiallycontrolled distribution of cross-linking.

In some embodiments, the incorporation of the additive can be performedby diffusion of the additive into already consolidated polymericmaterial. Such an additive-doped polymeric material doped by diffusioncan be extracted on one or more surface(s) by exposing to hightemperature to obtain a polymeric material with a spatially controlleddistribution of additive. One or more additive can be antioxidant(s).One additive can be vitamin E.

In another embodiment, the invention provides methods of makingadditive-doped polymeric material comprising: (a) doping a consolidatedpolymeric material with antioxidant(s) by diffusion below or above themelting point; (b) exposing one or more surface(s) of the additive-dopedpolymeric material to high temperature; and (c) cooling the heatedconsolidated additive-doped polymeric material; thereby forming apolymeric material with a spatially controlled distribution of additive.One or more additive can be antioxidant(s). One additive can be vitaminE.

In one embodiment, the invention provides methods of making across-linked additive-doped polymeric material with a spatialdistribution of cross-linking comprising: (a) consolidating thepolymeric material; (b) doping the polymeric material with one or moreadditive; (c) exposing one or more surface(s) of the consolidatedadditive-doped polymeric material to high temperature; (d) cooling theheated consolidated additive-doped polymeric material; and (e)irradiating the high temperature extracted consolidated additive-dopedpolymeric material thereby forming a cross-linked additive-blendedpolymeric material with a spatially controlled distribution ofcross-linking. One or more additive can be antioxidant(s). One additivecan be vitamin E.

In one embodiment, the invention provides methods of making across-linked additive-doped medical implant with a spatial distributionof cross-linking comprising: (a) consolidating the polymeric material;(b) machining the consolidated polymeric material; thereby forming amedical implant preform; (c) doping the medical implant preform with oneor more additive; (d) exposing one or more surface(s) of theconsolidated additive-doped medical implant preform to high temperature;(e) cooling the heated medical implant preform; (f) irradiating the hightemperature extracted medical implant preform thereby forming a medicalimplant with a spatially controlled distribution of cross-linking. Oneor more additive can be antioxidant(s). One additive can be vitamin E.

In one embodiment, the invention provides methods of making across-linked additive-doped medical implant with a spatial distributionof cross-linking comprising: (a) consolidating the polymeric material;(b) machining the consolidated polymeric material; thereby forming amedical implant preform; (c) doping the medical implant preform with oneor more additive; (d) exposing one or more surface(s) of theconsolidated additive-doped medical implant preform to high temperature;(e) cooling the heated medical implant preform; (f) machining the hightemperature extracted medical implant preform; thereby forming a medicalimplant; and (g) irradiating the medical implant; thereby forming amedical implant with a spatially controlled distribution ofcross-linking. One or more additive can be antioxidant(s). One additivecan be vitamin E.

In one embodiment, the invention provides methods of making across-linked additive-doped polymeric material with a spatialdistribution of cross-linking comprising: (a) blending one or moreadditive with the polymeric material; (b) consolidating theadditive-blended polymeric material; (c) doping the polymeric materialwith one or more additive; d) exposing one or more surface(s) of theconsolidated additive-blended and additive-doped polymeric material tohigh temperature; (d) cooling the heated consolidated additive-blendedand additive-doped polymeric material it to room temperature; and (e)irradiating the high temperature extracted consolidated additive-blendedand additive-doped polymeric material thereby forming a cross-linkedadditive-blended polymeric material with a spatially controlleddistribution of cross-linking. One or more additive can beantioxidant(s). One additive can be vitamin E.

In one embodiment, the invention provides methods of making across-linked additive-doped medical implant with a spatial distributionof cross-linking comprising: (a) blending one or more additive with thepolymeric material; (b) consolidating the additive-blended polymericmaterial; (c) machining the additive-blended polymeric material, therebyforming a medical implant preform; (d) doping the medical implantpreform with one or more additive; (d) exposing one or more surface(s)of the medical implant preform to high temperature; (e) cooling theheated medical implant preform; and (f) irradiating the high temperatureextracted medical implant preform; thereby forming a medical implantwith a spatially controlled distribution of cross-linking. One or moreadditive can be antioxidant(s). One additive can be vitamin E.

In one embodiment, the invention provides methods of making across-linked additive-doped medical implant with a spatial distributionof cross-linking comprising: (a) blending one or more additive with thepolymeric material; (b) consolidating the additive-blended polymericmaterial; (c) machining the additive-blended polymeric material, therebyforming a medical implant preform; (d) doping the medical implantpreform with one or more additive; (e) exposing one or more surface(s)of the medical implant preform to high temperature; (f) cooling theheated medical implant preform; (g) machining the medical implantpreform; thereby forming a medical implant; and (h) irradiating the hightemperature extracted medical implant; thereby forming a medical implantwith a spatially controlled distribution of cross-linking. One or moreadditive can be antioxidant(s). One additive can be vitamin E.

In another embodiment, the invention provides methods of makingadditive-containing polymeric material comprising: (a) blending one ormore additive with polymeric material; (b) consolidating theadditive-blended polymeric material; (c) exposing one or more surface(s)of the additive the consolidated material to high temperature whilesimultaneously using a doping source to diffuse additive from one ormore surface(s); (d) cooling the material; thereby forming a polymericmaterial with a spatially controlled distribution of additive.

In another embodiment, the invention provides methods of makingantioxidant containing polymeric material comprising: (a) blending oneor more antioxidant(s) with polymeric material; (b) consolidating theantioxidant-blended polymeric material; (c) exposing the consolidatedpolymeric material to high temperature, simultaneously using a dopingsource to diffuse antioxidant(s) from one or more surface(s); (d)cooling the material; thereby forming a polymeric material with aspatially controlled distribution of antioxidant(s).

In any of the embodiments, the doping source can be a consolidatedpolymeric material containing one or more additive that is contactedwith the desired surface(s) of the polymeric material. The doping sourcecan also be a layer of additive previously contacted with the polymericmaterial. The doping source can be a bath of additive in pure form, asmixtures or as solutions or emulsions in solvent. The doping source canbe the additive stored in the pores of a porous second material, whichcan be polymeric, metallic or ceramic.

In another embodiment, the invention provides methods of makingadditive-containing cross-linked polymeric material comprising: (a)blending one or more additive with polymeric material; (b) consolidatingthe additive-blended polymeric material; (c) exposing one or moresurface(s) of the additive-blended and consolidated polymeric materialat high temperature while simultaneously using a doping source todiffuse additive from one or more surface(s); (d) cooling the material;(e) irradiating the high temperature extracted additive-containingpolymeric material; thereby forming a polymeric material with aspatially controlled distribution of cross-links.

In another embodiment, the invention provides methods of makingantioxidant-containing cross-linked polymeric material comprising: (a)blending one or more antioxidant(s) with polymeric material; (b)consolidating the antioxidant-blended polymeric material; (c) exposingone or more surface(s) of the antioxidant-blended and consolidatedpolymeric material at high temperature while simultaneously using adoping source to diffuse antioxidant(s) from one or more surface(s); (d)cooling the material; (e) irradiating the high temperature extractedantioxidant-containing polymeric material; thereby forming a polymericmaterial with a spatially controlled distribution of cross-links.

In another embodiment, the invention provides methods of making vitaminE-containing cross-linked polymeric material comprising: (a) blendingvitamin E with polymeric material; (b) consolidating the vitaminE-blended polymeric material; (c) exposing one or more surface(s) of thevitamin E-blended and consolidated polymeric material at hightemperature while simultaneously using a doping source to diffuseantioxidant(s) from one or more surface(s); (d) cooling the material;(e) irradiating the high temperature extracted vitamin E-containingpolymeric material; thereby forming a polymeric material with aspatially controlled distribution of cross-links.

In another embodiment, the invention provides methods of makingadditive-containing cross-linked medical implant comprising: (a)blending one or more additive with polymeric material; (b) consolidatingthe additive-blended polymeric material; (c) machining the polymericmaterial; thereby forming a medical implant preform; (d) exposing one ormore surface(s) of the additive-blended medical implant preform at hightemperature while simultaneously using a doping source to diffuseadditive from one or more surface(s); (e) cooling the preform; and (f)irradiating the high temperature extracted medical implant preform;thereby forming a medical implant with a spatially controlleddistribution of cross-links.

In another embodiment, the invention provides methods of makingantioxidant-containing cross-linked medical implant comprising: (a)blending one or more antioxidant(s) with polymeric material; (b)consolidating the antioxidant-blended polymeric material; (c) machiningthe polymeric material; thereby forming a medical implant preform; (d)exposing one or more surface(s) of the antioxidant-blended medicalimplant preform at high temperature while simultaneously using a dopingsource to diffuse antioxidant(s) from one or more surface(s); (e)cooling the preform; and (f) irradiating the high temperature extractedmedical implant preform; thereby forming a medical implant with aspatially controlled distribution of cross-links.

In another embodiment, the invention provides methods of making vitaminE-containing cross-linked medical implant comprising: (a) blendingvitamin E with polymeric material; (b) consolidating the vitaminE-blended polymeric material; (c) machining the polymeric material;thereby forming a medical implant preform; (d) exposing one or moresurface(s) of the vitamin E-blended medical implant preform at hightemperature while simultaneously using a doping source to diffusevitamin E from one or more surface(s); (e) cooling the preform; and (f)irradiating the high temperature extracted medical implant preform;thereby forming a medical implant with a spatially controlleddistribution of cross-links.

In any of the embodiments, more than one antioxidant or additive can beblended with or diffused into the polymeric material. The purpose of theaddition of various components can be different, for instance oneadditive can be used in creating the spatially controlled distributionof cross-links after irradiation due to its anticross-linking abilityand another additive can be used to impart oxidation resistance.

In another embodiment, the invention provides methods of makingadditive-containing cross-linked medical implant comprising: (a)blending one or more additive with polymeric material; (b) consolidatingthe additive-blended polymeric material; (c) machining the polymericmaterial; thereby forming a medical implant preform; (d) exposing one ormore surface(s) of the additive-blended medical implant preform at hightemperature while simultaneously using a doping source to diffuseadditive from one or more surface(s); (e) cooling the preform; (f)machining the high temperature extracted medical implant preform;thereby forming a medical implant; and (g) irradiating the medicalimplant; thereby forming a medical implant with a spatially controlleddistribution of cross-links.

In another embodiment, the invention provides methods of makingantioxidant-containing cross-linked medical implant comprising: (a)blending one or more antioxidant(s) with polymeric material; (b)consolidating the antioxidant-blended polymeric material; (c) machiningthe polymeric material; thereby forming a medical implant preform; (d)exposing one or more surface(s) of the antioxidant-blended medicalimplant preform at high temperature while simultaneously using a dopingsource to diffuse antioxidant(s) from one or more surface(s); (e)cooling the preform; (f) machining the high temperature extractedmedical implant preform; thereby forming a medical implant; and (g)irradiating the medical implant; thereby forming a medical implant witha spatially controlled distribution of cross-links.

In another embodiment, the invention provides methods of making vitaminE-containing cross-linked medical implant comprising: (a) blendingvitamin E with polymeric material; (b) consolidating the vitaminE-blended polymeric material; (c) machining the polymeric material;thereby forming a medical implant preform; (d) exposing one or moresurface(s) of the vitamin E-blended medical implant preform at hightemperature while simultaneously using a doping source to diffusevitamin E from one or more surface(s); (e) cooling; (f) machining thehigh temperature extracted medical implant preform; thereby forming amedical implant; and (g) irradiating the medical implant; therebyforming a medical implant with a spatially controlled distribution ofcross-links.

In any of the embodiments, after consolidation, the polymeric materialcan be heated to below or above its melting temperature to relieve theresidual stresses from consolidation. For example, this temperature canbe one or more temperature(s) between about 60° C. to about 200° C.,more preferably about 100° C. to about 130° C. The duration for heatingcan be from 1 minute to more than 36 hours, more preferably from 1 hourto about 24 hours, most preferably about 8 hours. At this step, thetemperature(s) and heating duration, to which the polymeric material isexposed, can be such that there is no extraction from the surfaces.Alternatively, the heating can be done with the surfaces covered toprevent extraction. If the heating is done at a temperature and aduration at which there was extraction from the surface(s), thepolymeric material can be machined to remove the extracted layer.

In any of the embodiments, the additive blended or diffused into thepolymer can comprise 0.001 wt % to more than 50 wt % of the polymericmaterial, preferably between 0.1 wt % and 5 wt %, more preferably about1 wt %. In any of the embodiments, one or more antioxidant(s) cancomprise 0.001 wt % to 100 wt % of the additive.

In any of the embodiments, the polymeric material at the beginning ofthe process can be in any unconsolidated form such as extrudate, pellet,resin powder, flakes, liquid or gel. The polymeric material can beconsolidated by any polymer consolidation technique such as compressionmolding, ram extrusion, extrusion, hot or cold isostatic pressing,injection molding, direct compression molding. In the case of ultrahighmolecular weight polyethylene, compression molding is the most commonlyused technique, therefore consolidation can be used interchangeably withcompression molding, but this does not limit the invention toconsolidation by compression molding. The details of the consolidationprocess is described in the definitions; the consolidation process canbe optimized in a manner clear to those skilled in the art to obtainconsolidated polymeric material with high integrity, mechanical strengthand toughness.

In any of the embodiments, the consolidated and/or machined forms of thepolymeric material can have thickness from 100 microns to 100centimeters, preferably between 1 millimeter to 20 centimeters, mostpreferably about 8 millimeters. The thickness of the polymeric materialcan vary within the consolidated and/or machined form depending on thedesign of the medical implant preform and medical implant.

In any of the embodiments, the high temperature, to which polymericmaterial is exposed for extraction of additive, can be from 200° C. to500° C., more preferably from 220° C. to 300° C., most preferably about290° C. The heating duration, which may include the time for thepolymeric material to reach equilibrium at the extraction temperature,can be between 1 minute and 100 hours, more preferably between 1 hourand 4 hours, most preferably about 3 hours.

In any of the embodiments, the heating environment, for example for hightemperature exposure, can be an inert gas, a non-inert gas, air, vacuum,a liquid, a liquid with gas bubbled through, a liquid saturated withgas, a supercritical fluid or mixtures thereof. Inert gases can benitrogen or argon or any other inert gas. The pressure(s) during anystep in processing can be between 10⁻⁹ atmospheres and 10000atmospheres, for example between 10⁻⁶ atmospheres and 200 atmospheres.During high temperature extraction, full vacuum, partial vacuum, ambientpressure or pressurized atmospheres can be used.

In any of the embodiments, machining of the polymeric material, medicalimplant preform or medical implant shapes can be performed at any stepof processing before packaging and sterilization of the implant. In anyof the embodiments, the medical implant can be packaged and terminallysterilized in appropriate packaging. Sterilization can be done by gassterilization methods such as ethylene oxide gas or gas plasmasterilization or ionizing radiation such as gamma sterilization.

In any of the embodiments, medical devices could be a permanent medicalimplant or a non-permanent medical implant. Medical devices selectedfrom the group consisting of acetabular liner, shoulder glenoid,patellar component, finger joint component, ankle joint component, elbowjoint component, wrist joint component, toe joint component, bipolar hipreplacements, tibial knee insert, tibial knee inserts with reinforcingmetallic and polyethylene posts, intervertebral discs, interpositionaldevices for any joint, sutures, tendons, heart valves, stents, vasculargrafts. The medical implant can be a non-permanent medical device, forexample, a catheter, a balloon catheter, a tubing, an intravenoustubing, or a suture.

In any of the embodiments, other extraction methods such as extractionof the additive in a liquid, gas or fluid medium can be used before orafter high temperature exposure. For example, extraction using organicsolvents such as hexane, heptane or ethanol can be used. Alternatively,an aqueous medium such as an aqueous emulsion or solution can be used.These extraction methods can be used before or after high temperatureexposure to modify the concentration profiles of additive. For example,the concentration of one or more additive can be lowered in the surfaceregions of the polymeric material or medical implant preform or medicalimplant.

In any of the embodiments, consolidated polymeric material could bemasked during high temperature exposure or other extraction methods.Masking area could be anywhere from 0% to 99% of the total surface area.Parts of the same surface, for example articular surface, can be masked.In any of the embodiments, material used for masking could be anymaterial whose dimensional change upon heating for high temperatureexposure is small. Preferably, the masking material does not melt belowor at the temperature used during high temperature exposure. If themasking material melts, it preferably does not exude or leach any partsinto the polymeric material being masked. Examples of such materials canbe metals such as aluminum, copper, iron or any other material whichfits this description. The masking material can be of any practicallyfeasible thickness, from 1 microns to 1 meter, preferably 100 microns to500 microns.

In any of the embodiments, the steps of a process outlined in a methodcan be repeated once or many times. For example, high temperatureexposure and cooling steps can be repeated. In any of the embodiments,heating and cooling can be applied at the same time to different partsof the polymeric material, medical implant preform or medical implant.For example, a medical implant preform can be cooled from a reservoir onits backside while being exposed to high temperature on its intendedarticular surfaces for extraction.

In any of the embodiments, polymeric material, medical implant preformor medical implants can be annealed after irradiation to redistributeone or more additive throughout the material. This annealing step can beused for the homogenization of the additive and can be performed belowor above the melting point of the polymeric material. Annealingtemperature can be between room temperature to 500° C., preferablybetween 100 and 170° C., most preferably 130° C. After this annealingstep, the concentration profile of the additive does not need to behomogeneous.

In any of the embodiments, irradiation can be done by a gamma orelectron beam irradiation. In any of the embodiments, irradiationtemperature could be anywhere between 0° C. to 320° C., preferablybetween 25° C. and 130° C., most preferably between 40° C. and 130° C.Irradiation at elevated temperatures (warm irradiation), for exampleabove 90° C., can have advantages such as increased cross-linking andincreased grafting of the additive onto the polymer, decreasing elution.In any of the embodiments, irradiation environment could be nitrogen,argon or any other inert gas, air, oxygen or any other gas. In any ofthe embodiments, pressure during irradiation could be anywhere between10⁻⁹ atm to 20 atm preferably between 10⁻⁶ atm to 1 atm. In any of theembodiments, total radiation dose could be between 1 kGy to 10000 kGy,preferably between 25 kGy to 250 kGy, most preferably about 200 kGy.Irradiation dose per pass can be varied, it can be between 0.00001kGy/pass to 10000 kGy/pass, preferably about 25 kGy/pass to 100kGy/pass. In the case of a gamma irradiation, the dose rate can bebetween 0.0000001 kGy/min to 10000 kGy/min, preferably about 0.01kGy/min. The irradiation may be carried out in a sensitizing atmosphere.This may comprise a gaseous substance which is of sufficiently smallmolecular size to diffuse into the polymer and which, on irradiation,acts as a polyfunctional grafting moiety. Examples include substitutedor unsubstituted polyunsaturated hydrocarbons; for example, acetylenichydrocarbons such as acetylene; conjugated or unconjugated olefinichydrocarbons such as butadiene and (meth)acrylate monomers; sulphurmonochloride, with chloro-tri-fluoroethylene (CTFE) or acetylene beingparticularly preferred. By “gaseous” is meant herein that thesensitizing atmosphere is in the gas phase at the irradiationtemperature. In the case of electron beam irradiation, the beam energycould be between 500 keV and 20 MeV, preferably 10 MeV.

In any of embodiments, 0 millimeters to 10 centimeters of the materialcould be machined off from the extracted surface to get the desiredgeometry and dimensions of the medical device, preferably 0.1millimeters to 1.5 millimeters of the material is machined off from theextracted surface.

In any of the embodiments, the medical implant is packaged andsterilized by ionizing radiation or gas sterilization, thereby forming asterile and cross-linked oxidation-resistant medical implant.

In any of the embodiments, doping source could be blended polyethylenewith antioxidant(s), polyethylene doped with antioxidant (s) viadiffusion, free antioxidant(s), porous ceramic doped with antioxidant(s)via diffusion, porous polyethylene doped with antioxidant(s) viadiffusion, porous polytetrafluoroethylene (e.g., Teflon®) doped withantioxidant(s) via diffusion.

In any of the embodiments if blended polyethylene with antioxidant(s) isused as a doping source, the concentration of antioxidant(s) could beanywhere between 0.01 wt % to 50 wt %, preferably between 0.5 wt % to 10wt %.

In any of the embodiments, if free antioxidant(s) is used as a dopingsource, concentration could be 100% or it could be diluted with ethanolor any other solvent to reduce the concentration.

In any of the embodiments, doped porous ceramic, doped porouspolyethylene, doped porous polytetrafluoroethylene, or dopedpolyethylene is obtained by keeping the doping material inantioxidant(s) solution for anywhere between 1 min to 100 days,preferably between 3 hours to 18 hours.

In any of the embodiments, the consolidated polymeric material orperform could be dipped in antioxidant(s) solution of concentrationbetween 0.1 wt % to 100 wt %, preferably between 50 wt % to 100 wt %,before the extraction process.

A layer of blended polyethylene with antioxidant(s) is defined asconsolidated polymeric material with uniform concentration ofantioxidant(s). Therefore sequential layers of different or sameantioxidant(s) concentration may be used to diffuse antioxidant(s)through different layers towards the back surface of medical implant orconsolidated polymeric material. In any of the embodiments, when blendedpolyethylene is used as doping source, the number of sequential layersused as a doping source could be anywhere between 2 to 100 layerspreferably between 2 to 4 layers.

In any of the embodiments, when blended polyethylene is used as a dopingsource, thickness of doping layers could be anywhere between 1 micron to100 centimeters, preferably between 1 millimeters to 15 millimeters whenblended polyethylene is used as doping source

In any of the embodiments, doping source could be used throughout theduration of extraction or it could be a fraction of the extractionduration. Duration of doping source used could be anywhere between 1minutes to 100 hours, preferably between 60 minutes to 8 hours.

In some embodiments, the invention comprises methods of making implantsmade out of surface extracted, cross-linked polymeric material. In someembodiments, the invention comprises methods of making implants made outof antioxidant-blended, surface extracted, cross-linked polymericmaterial. In some embodiments, the invention describes methods ofproviding wear resistant antioxidant-containing polymeric materials. Insome embodiments, the invention describes methods of providing oxidationresistant antioxidant-containing polymeric materials.

These and other features, aspects, and advantages of the presentinvention will become better understood upon consideration of thefollowing detailed description, drawings and claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic of the high temperature extraction of vitamin Efrom vitamin E-incorporated polymeric block (not drawn toscale—measurements in mm.).

FIG. 2 is a vitamin E concentration profile from the surface towards thebulk of a UHMWPE block extracted at 290° C. for 290 minutes in aconvection oven in nitrogen.

FIG. 3 is a vitamin E concentration profile of vitamin E-blended UHMWPEblocks extracted at high temperature at 290° C. for 290 minutes beforeand after irradiation at 175 kGy.

FIG. 4 is a schematic of how samples were obtained for cross-linkdensity from the extracted and irradiated samples. Not drawn toscale—measurements in mm.)

FIG. 5 is an average wear rate for first 1000 micron depth for extractedmaterial irradiated to 175 kGy.

FIG. 6 is a vitamin E concentration profile of samples having initialconcentration of 2% and 0.75% respectively, extracted in vacuum oven at220° C. for 16 hours.

FIG. 7 is a schematic of surface extraction of vitamin E from vitamin Eincorporated polymer block in an oven and microtomed sections obtainedfor FTIR (not drawn to scale—measurements in mm.).

FIG. 8 is a vitamin E concentration profile of samples having initialconcentration of 1 wt % vitamin E which were kept in an oven in air at220° C. for 60 minutes and 105 minutes respectively.

FIG. 9 is a vitamin E concentration profile of samples having initialconcentration of 1% vitamin E which were kept in a convection oven inair at 220° C. for 30 minutes and 60 minutes respectively.

FIG. 10 is a vitamin E concentration profile of samples having initialconcentration of 1% vitamin E which were kept in a convection oven innitrogen at 290° C. for 90 minutes, 120 minutes and 210 minutesrespectively.

FIG. 11 shows vitamin E concentration profiles of 1 wt % vitamin Eblended UHMWPE after exposure to 220° C. in vacuum (2×10⁻⁶ atm argon)for 25, 50, 105, 180 or 240 minutes.

FIG. 12 shows vitamin E concentration profiles of 1 wt % blended UHMWPEafter exposure to 180° C., 250° C. or 270° C. for 90 minutes.

FIG. 13 shows vitamin E concentration profiles of 1 wt % vitaminE-blended UHMWPE after exposure to 200° C. or 230° C. for 60 minutes inair.

FIG. 14 shows vitamin E concentration profiles of 0.75 wt % and 1 wt %vitamin E-blended UHMWPE's exposed to 290° C. for 210 minutes innitrogen.

FIG. 15 shows vitamin E concentration profiles of 1 wt % vitamin Eblended UHMWPE cubes exposed to 290° C. for 90 minutes without maskingand with masking of all but one surface.

FIG. 16 is a vitamin E concentration profile of 1 wt % vitamin E-blendedUHMWPE after exposure to 220° C. for 180 minutes continuous heatingversus 180 minutes during 15 minute heating/3 minute cooling cycles.

FIG. 17 is a vitamin E concentration profile of 1 wt % vitamin E blendedUHMWPE after exposure to 220° C. in vacuum (2×10⁻⁶ atm argon) for 105minutes and further extraction for 3 hours in a boiling aqueous Tween 20solution (20 wt %).

FIG. 18 is a vitamin E concentration profile of 1 wt % vitamin E blendedUHMWPE after exposure to 220° C. in vacuum (2×10⁻⁶ atm argon) for 105minutes and further extraction for 3 hours in a boiling hexane.

FIG. 19 is a vitamin E concentration of 1 wt % vitamin E-blended UHMWPEextracted using a 20 wt % Tween 20 solution in water followed by hightemperature exposure at 200° C. for 105 minutes in 2×10⁻⁶ atm (argon).

FIG. 20 is a vitamin E concentration profile of 1 wt % vitamin E-blendedUHMWPE exposed to 220° C. for 105 minutes, then extracted using a Tween20 solution followed by further exposure to 220° C. compared to 1 wt %vitamin E blended UHMWPE exposed to 220° C. alone for 105 minutes

FIG. 21 is a vitamin E concentration profile of 1 wt % vitamin E-blendedUHMWPE after exposure to 220° C. in vacuum (2×10⁻⁶ atm argon) for 105minutes followed by 3 hours boiling in ethanol followed by exposure to220° C. for 60 minutes.

FIG. 22 is a vitamin E concentration profile of a 0.3 wt % vitaminE-blended cube (10 mm-thick) which was exposed to 290° C. for 120minutes in contact with a 3 wt % vitamin E blended cube (contact at 10mm).

FIG. 23 shows a schematic of the high temperature extraction of vitaminE from exposed surface in oven with simultaneous doping of vitamin Efrom back surface through a doping medium (10 mm. cube) (Not drawn toscale—measurements in mm.).

FIG. 24 is a vitamin E concentration profile of a 0.3 wt % vitaminE-blended puck (10 mm-thick) which was exposed to 290° C. for 290minutes in contact with a 3 wt % vitamin E blended puck (contact at 10mm.) before and after irradiation to 175 kGy.

FIG. 25 shows the cross-link density of 0.3 wt % UHMWPE puck (10 mm.thick) irradiated to 175 kGy compared to the cross-link density of a 0.3wt % vitamin E-blended puck (10 mm.-thick) which was exposed to 290° C.for 290 minutes in contact with a 3 wt % vitamin E blended puck (contactat 10 mm.) also irradiated to 175 kGy.

FIG. 26 shows the vitamin E concentration profile of a 0.3 wt % vitaminE-blended cuboid (20 mm.-thick) which was exposed to nitrogen at 290° C.for 120 minutes and 210 minutes and was simultaneously contacted withvitamin E doped porous ceramic (contact at 20 mm.).

FIG. 27 shows the vitamin E concentration profile of a 0.3 wt % vitaminE-blended cube (10 mm.-thick) which was exposed to nitrogen at 290° C.for 30 minutes. Cube was dip-coated on 5 sides (x=10 mm.) with vitamin Eat room temperature before extraction in oven.

FIG. 28 shows the vitamin E concentration profile of a 0.3 wt % vitaminE-blended cube (10 mm.-thick) which was in contact with a 3 wt % vitaminE blended cube (contact at 10 mm.) and was exposed to 290° C. for 120minutes and 180 minutes respectively.

FIG. 29 shows the vitamin E concentration profile of samples havinginitial concentration of 0% and 0.3 wt % vitamin E respectively,extracted in convection oven in nitrogen at 290° C. for 180 minuteswhile in contact with a 3 wt % vitamin E blended cube (contact at 10mm.).

FIG. 30 shows a vitamin E concentration profile of samples havinginitial concentration 0.3 wt % vitamin E respectively, extracted inconvection oven in nitrogen at 290° C. for 180 minutes while in contactwith vitamin E blended cubes of 2 wt %, 3 wt % and 5 wt % vitamin Econcentration respectively (contact at 10 mm.).

FIG. 31 shows vitamin E index as a function of depth was compared forsurface extracted and back side vitamin E doped samples by changingnumber of layers used as a doping medium.

FIG. 32 shows a vitamin E concentration profile of samples havinginitial concentration 0.3 wt % vitamin E respectively, extracted inconvection oven in nitrogen at 290° C. for 150, 160 or 180 minutes whilein contact with vitamin E blended cubes with 5 wt % vitamin Econcentration (contact at 10 mm.).

DETAILED DESCRIPTION

The term ‘cross-linked’ refers to the state of a polymeric material witha cross-link density of at least 30 mol/m³. The cross-link density ismeasured by swelling a roughly 3×3×3 mm cube of polymeric material inxylene. The samples are weighed before swelling in xylene at 130° C. for2 hours and they are weighed immediately after swelling in xylene. Theamount of xylene uptake is determined gravimetrically, then converted tovolumetric uptake by dividing by the density of xylene (0.75 g/cm³). Byassuming the density of polyethylene to be approximately 0.94 g/cm³, thevolumetric swell ratio of cross-linked UHMWPE is then determined. Thecross-link density is calculated using the swell ratio as described inOral et al., Biomaterials 31: 7051-7060 (2010) and is reported inmol/m³. Thus, a substantially cross-linked polymeric material has across-link density of about 30 mol/m³ in at least one part of thepolymeric material. The term ‘highly cross-linked’ refers to the stateof a polymeric material with a cross-link density of about 100 mol/m³ inat least one part of the polymeric material. For example, an implantwith surfaces having a cross-link density of about 250 mol/m³, and thebulk regions having a cross-link density of about 60 mol/m³ would behighly cross-linked.

The term ‘wear resistant’ refers to the state of a polymeric materialwith a wear rate of less than 6 mg/million-cycles. The wear rate istested on cylindrical pins (diameter=9 mm, length=13 mm) on abidirectional pin-on-disc wear tester in undiluted bovine calf serum at2 Hz in a rectangular pattern (5 mm×10 mm) under variable load with amaximum of 440 lbs as described in Bragdon et al., (J Arthroplasty 16:658-665 (2001)). Initially, the pins are subjected to 0.5 million cycles(MC), after which they are tested to 1.25 million cycles withgravimetric measurements approximately every 0.125 MC. The wear rate isdetermined by the linear regression of the weight loss as a function ofnumber of cycles from 0.5 to 1.25 MC. The term “highly wear resistant”refers to the state of a polymeric material with a wear rate of lessthan 3 mg/million-cycles.

“Polymeric materials” or “polymers” includes polyethylene. For example,ultra-high molecular weight polyethylene (UHMWPE) refers to linearnon-branched chains of ethylene having molecular weights in excess ofabout 500,000, preferably above about 1,000,000, and more preferablyabove about 2,000,000. Often the molecular weights can reach about8,000,000 or more. By initial average molecular weight is meant theaverage molecular weight of the UHMWPE starting material, prior to anyirradiation. See U.S. Pat. No. 5,879,400, PCT/US99/16070, filed on Jul.16, 1999, and PCT/US97/02220, filed Feb. 11, 1997. The term“polyethylene article” or “polymeric article” or “polymer” generallyrefers to articles comprising any “polymeric material” disclosed herein.

“Polymeric materials” or “polymers” also includes hydrogels, such aspoly(vinyl alcohol), poly(acrylamide), poly(acrylic acid), poly(ethyleneglycol), blends thereof, or interpenetrating networks thereof, which canabsorb water such that water constitutes at least 1 to 10,000% of theiroriginal weight, typically 100 wt % of their original weight or 99% orless of their weight after equilibration in water.

“Polymeric material” or “polymer” can be in the form of resin, flakes,powder, consolidated stock, preform, implant, and can contain additivessuch as antioxidant(s). The “polymeric material” or “polymer” also canbe a blend of one or more of different resin, flakes or powdercontaining different concentrations of an additive such as anantioxidant. The blending of resin, flakes or powder can be achieved bythe blending techniques known in the art. The “polymeric material” alsocan be a consolidated stock of these blends.

The term ‘irradiation’ refers to exposing the polymeric material to atype of radiation source. Irradiation can be done by ultravioletirradiation sources, gamma irradiation sources, electron beamirradiation sources or X-ray irradiation sources or others. Radiationcross-linking and thermal treatment methods are further defined asfollows:

(i) Irradiation in the Molten State (IMS):

Melt-irradiation, or irradiation in the molten state (“IMS”), isdescribed in detail in U.S. Pat. No. 5,879,400. In the IMS process, thepolymer to be irradiated is heated to at or above its melting point.Then, the polymer is irradiated. Following irradiation, the polymer iscooled.

Prior to irradiation, the polymer is heated to at or above its meltingtemperature and maintained at this temperature for a time sufficient toallow the polymer chains to achieve an entangled state. A sufficienttime period may range, for example, from about 5 minutes to about 3hours. For UHMWPE, the polymer may be heated to a temperature betweenabout 145° C. and about 320° C., preferably about 150° C. to about 200°C.

The temperature of melt-irradiation for a given polymer depends on theDSC (measured at a heating rate of 10° C./min during the first heatingcycle) peak melting temperature (“PMT”) for that polymer. In general,the irradiation temperature in the IMS process is about 2° C. higherthan the PMT, more preferably between about 2° C. and about 20° C.higher than the PMT, and most preferably between about 5° C. and about10° C. higher than the PMT. The temperature in the IMS process can behigher, up to 320° C.

The total dose of irradiation also may be selected as a parameter incontrolling the properties of the irradiated polymer. In particular, thedose of irradiation can be varied to control the degree of cross-linkingand crystallinity in the irradiated polymer. The total dose may rangefrom about 0.1 MRad to about the irradiation level where the changes inthe polymer characteristics induced by the irradiation reach asaturation point. For instance, the high end of the dose range could be20 MRad for the melt-irradiation of UHMWPE, above which dose level thecross-link density and crystallinity are not appreciably affected withany additional dose. The preferred dose level depends on the desiredproperties that will be achieved following irradiation. Additionally,the level of crystallinity in polyethylene is a strong function ofradiation dose level. See Dijkstra et al., Polymer 30: 866-73 (1989).For instance with IMS irradiation, a dose level of about 20 Mrad woulddecrease the crystallinity level of UHMWPE from about 55% to about 30%.This decrease in crystallinity may be desirable in that it also leads toa decrease in the elastic modulus of the polymer and consequently adecrease in the contact stress when a medical prosthesis made out of theIMS-treated UHMWPE gets in contact with another surface during in vivouse. Lower contact stresses are preferred to avoid failure of thepolymer through, for instance, subsurface cracking, delamination,fatigue, etc. The increase in the cross-link density is also desirablein that it leads to an increase in the wear resistance of the polymer,which in turn reduces the wear of the medical prostheses made out of thecross-linked polymer and substantially reduces the amount of wear debrisformed in vivo during articulation against a counterface. In general,the melt-irradiation and subsequent cooling will lead to a decrease inthe crystallinity of the irradiated polymer.

(ii) Warm Irradiation:

Warm irradiation is described in detail in PCT International ApplicationNo. WO 97/29793. In the warm irradiation process, a polymer is providedat a temperature above room temperature and below the meltingtemperature of the polymer. Then, the polymer is irradiated. In oneembodiment of warm irradiation, termed warm irradiation adiabaticmelting (WIAM) the polymer may be irradiated at a high enough total doseand/or a high enough dose rate to generate enough heat in the polymer toresult in at least a partial melting of the crystals of the polymer.

The adiabatic temperature rise depends on the dose level, level ofinsulation, and/or dose rate. Exemplary ranges of acceptable totaldosages are disclosed in greater detail in WO 97/29793.

In some embodiments, UHMWPE is used as the starting polymer. In oneembodiment, the total dose is about 0.5 MRad to about 1,000 Mrad. Inanother embodiment, the total dose is about 1 MRad to about 100 MRad. Inyet another embodiment, the total dose is about 4 MRad to about 30 MRad.In still other embodiments, the total dose is about 20 MRad or about 15MRad.

The polymer may be provided at any temperature below its melting pointand above room temperature. The temperature selection depends on thespecific heat and the enthalpy of melting of the polymer and the totaldose level that will be used. The equation provided in PCT InternationalApplication No. WO 97/29793 may be used to calculate the preferredtemperature range with the criterion that the final temperature ofpolymer maybe below or above the melting point. Preheating of thepolymer to the desired temperature may be done in an inert or non-inertenvironment.

Exemplary ranges of acceptable total dosages are disclosed in greaterdetail in PCT International Application No. WO 97/29793. In oneembodiment, the UHMWPE is preheated to about 20° C. to about 135° C. Inone embodiment, the UHMWPE is preheated to about 100° C. to just belowthe melting temperature of the polymer. In another embodiment, theUHMWPE is preheated to a temperature of about 100° C. to about 135° C.In yet other embodiments, the polymer is preheated to about 120° C. orabout 130° C.

In general terms, the pre-irradiation heating temperature of the polymercan be adjusted based on the peak melting temperature (PMT) measure onthe DSC at a heating rate of 10° C./minute during the first heat. In oneembodiment, the polymer is heated to about 20° C. to about PMT. Inanother embodiment, the polymer is preheated to about 40° C., 50° C.,60° C., 70° C., 80° C. or 90° C. In another embodiment, the polymer isheated to about 100° C. In another embodiment, the polymer is preheatedto about between 30° C. below PMT and 2° C. below PMT. In anotherembodiment, the polymer is preheated to about 12° C. below PMT.

In the WIAM embodiment of warm irradiation, the temperature of thepolymer following irradiation is at or above the melting temperature ofthe polymer. Exemplary ranges of acceptable temperatures followingirradiation are disclosed in greater detail in WO 97/29793. In oneembodiment, the temperature following irradiation is about roomtemperature to PMT, or about 40° C. to PMT, or about 100° C. to PMT, orabout 110° C. to PMT, or about 120° C. to PMT, or about PMT to about200° C. In another embodiment, the temperature following irradiation isabout 145° C. to about 190° C. In yet another embodiment, thetemperature following irradiation is about 146° C. to about 190° C. Instill another embodiment, the temperature following irradiation is about150° C.

The dose rate of irradiation also may be varied to achieve a desiredresult. The dose rate is a prominent variable in the warm irradiationprocess. In the case of warm irradiation of UHMWPE, higher dose rateswould provide the least amount of reduction in toughness and elongationat break. The preferred dose rate of irradiation would be to administerthe total desired dose level in one pass under the electron-beam. Onecan also deliver the total dose level with multiple passes under thebeam, delivering a (equal or unequal) portion of the total dose at eachtime. This would lead to a lower effective dose rate.

In some embodiments, double-sided irradiation may be used to achievedesired penetration depth and dose profiles in the polymeric material.

Ranges of acceptable dose rates are exemplified in greater detail in PCTInternational Application No. WO 97/29793. In general, the dose rateswill vary between 0.5 MRad/pass and 50 MRad/pass. The upper limit of thedose rate depends on the resistance of the polymer tocavitation/cracking induced by the irradiation.

Depending on the polymer or polymer alloy used, and whether the polymerwas irradiated below its melting point, there may be residual freeradicals left in the material following the irradiation process. Apolymer irradiated below its melting point with ionizing radiationcontains cross-links as well as long-lived trapped free radicals. Someof the free radicals generated during irradiation become trapped atcrystalline lamellae surfaces (see Kashiwabara, H. S. Shimada, and Y.Hori, Free Radicals and Crosslinking in Irradiated Polyethylene, Radiat.Phys. Chem., 1991, 37(1): p. 43-46) leading to oxidation-inducedinstabilities in the long-term (see Jahan, M. S. and C. Wang, CombinedChemical and Mechanical Effects on Free radicals in UHMWPE Joints DuringImplantation, Journal of Biomedical Materials Research, 1991, 25: p.1005-1017; Sutula, L. C., et al., Impact of gamma sterilization onclinical performance of polyethylene in the hip”, Clinical OrthopedicRelated Research, 1995, 3129: p. 1681-1689.) The elimination of theseresidual, trapped free radicals through melt annealing is, therefore,desirable in precluding long-term oxidative instability of the polymer(see Jahan M. S. and C. Wang, “Combined chemical and mechanical effectson free radicals in UHMWPE joints during implantation”, Journal ofBiomedical Materials Research, 1991, 25: p. 1005-1017; Sutula, L. C., etal., “Impact of gamma sterilization on clinical performance ofpolyethylene in the hip”, Clinical Orthopedic Related Research, 1995,319: p. 28-4).

If there are residual free radicals remaining in the material, these maybe reduced to substantially undetectable levels, as measured by electronspin resonance or other tests, through annealing of the polymer abovethe melting point of the polymeric system used. The melt annealingallows the residual free radicals to recombine with each other. If for agiven system the preform does not have substantially any detectableresidual free radicals following irradiation, then a melt annealing stepmay be omitted. Also, if for a given system, the concentration of theresidual free radicals is low enough to not lead to degradation ofdevice performance, the melt annealing step may be omitted. In apolymeric material where at least one additive is an antioxidant, amelting step after irradiation may be omitted or shortened. In apolymeric material where at least one additive is an antioxidant, anannealing step after irradiation may be omitted or shortened. Also, in apolymeric material where at least one additive is an antioxidant,reduction of the residual free radicals caused by radiation may not benecessary for oxidation resistance.

In some of the lower molecular weight and lower density polyethylenes,the residual free radicals may recombine with each other even at roomtemperature over short periods of time, for example, few hours to fewdays, to few months. In such cases, the subsequent melt-annealing may beomitted if the increased crystallinity and modulus resulting from theirradiation is preferred. Otherwise, the subsequent melt-annealing maybe carried out to decrease the crystallinity and modulus. In the casewhere melt annealing is omitted, the irradiated preform can be directlymachined into the final medical device. The subsequent melt-annealingmay also be omitted if the polymer contains enough antioxidant toprevent oxidation in the long-term.

The reduction of free radicals to the point where there aresubstantially no detectable free radicals can be achieved by heating thepolymer to above the melting point. The heating provides the moleculeswith sufficient mobility so as to eliminate the constraints derived fromthe crystals of the polymer, thereby allowing essentially all of theresidual free radicals to recombine. Preferably, the polymer is heatedto a temperature between the peak melting temperature (PMT) and 500° C.,more preferably between about 3° C. above PMT and 500° C., morepreferably between about 10° C. above PMT and 50° C. above PMT, morepreferably between about 10° C. and 12° C. above PMT and most preferablyabout 15° C. above PMT.

During melt annealing of UHMWPE, the polymer is heated to a temperatureof about 137° C. to about 320° C., more preferably about 140° C. toabout 320° C., more preferably yet about 140° C. to about 190° C., morepreferably yet about 145° C. to about 300° C., more preferably yet about145° C. to about 190° C., more preferably yet about 146° C. to about190° C., and most preferably about 150° C. Preferably, the temperaturein the heating step is maintained for about 0.5 minutes to about 24hours, more preferably about 1 hour to about 3 hours, and mostpreferably about 2 hours. The heating can be carried out, for example,in air, in an inert gas, e.g., nitrogen, argon or helium, in asensitizing atmosphere, for example, acetylene, or in a vacuum. It ispreferred that for the longer heating times, that the heating be carriedout in an inert gas or under vacuum to avoid in-depth oxidation.

In certain embodiments, there may be a tolerable level of residual freeradicals in which case, the post-irradiation annealing can also becarried out below the melting point of the polymer. Alternatively,annealing below the melting point can be performed to reduce freeradicals to undetectable levels by combination with mechanicaldeformation after irradiation or annealing under pressure at elevatedtemperature.

During below the melt annealing of UHMWPE, the polymer is heated to atemperature of about 70° C. to about 300° C., more preferably about 100°C. to about 135° C., more preferably yet about 120° C. to about 130° C.,most preferably about 125° C. In cases where the temperature is abovethe melting temperature of the polymeric material at ambient pressure,the pressure may be increased to elevate the melting temperature andmaintain the polymeric material below the melting temperature.Preferably, the temperature in the heating step is maintained for about0.5 minutes to about 24 hours, more preferably about 1 hour to about 3hours, and most preferably about 2 hours. The heating can be carriedout, for example, in air, in an inert gas (e.g., nitrogen, argon orhelium), in a sensitizing atmosphere (e.g., acetylene), or in a vacuum.It is preferred that for the longer heating times, that the heating becarried out in an inert gas or under vacuum to avoid in-depth oxidation.

(iii) Sequential Irradiation:

The polymer is irradiated in a sequential manner. With e-beam theirradiation is carried out with multiple passes under the beam and withgamma radiation the irradiation is carried out in multiple passesthrough the gamma source. Optionally, the polymer is thermally treatedin between each or some of the irradiation passes. The thermal treatmentcan be annealing below the melting point, at the melting point or abovethe melting point of the polymer of the polymer. The irradiation at anyof the steps can be warm irradiation, cold irradiation, or meltirradiation, as described above. For example the polymer is irradiatedwith 30 kGy at each step of the cross-linking and it is first heated toabout 120° C. and then annealed at about 120° C. for about 5 hours aftereach irradiation cycle.

The term “blending” generally refers to mixing of a polyolefin in itspre-consolidated form with an additive. If both constituents are solid,blending can be done dry or by using a third component such as a liquidto mediate the mixing of the two components, after which the liquid isremoved by evaporating (‘solvent blending’). If the additive is liquid,for example α-tocopherol, then the solid can be mixed with largequantities of liquid, then diluted down to desired concentrations withthe solid polymer to obtain uniformity in the blend. In the case wherean additive is also an antioxidant, for example vitamin E, orα-tocopherol, then blended polymeric material is also antioxidant-doped.Polymeric material, as used herein, also applies to blends of apolyolefin and a plasticizing agent, for example a blend of UHMWPE resinpowder blended with α-tocopherol and consolidated. Polymeric material,as used herein, also applies to blends of an additive, a polyolefin anda plasticizing agent, for example UHMWPE soaked in α-tocopherol.

In one embodiment, UHMWPE flakes are blended with α-tocopherol;preferably the UHMWPE/α-tocopherol blend is heated to diffuse theα-tocopherol into the flakes. The UHMWPE/α-tocopherol blend is furtherblended with virgin UHMWPE flakes to obtain a blend of UHMWPE flakeswhere some flakes are poor in α-tocopherol and others are rich inα-tocopherol. This blend is then consolidated and irradiated. Duringirradiation the α-tocopherol poor regions are more highly cross-linkedthan the α-tocopherol poor regions. Following irradiation the blend ishomogenized to diffuse α-tocopherol from the α-tocopherol rich toα-tocopherol poor regions and achieve oxidative stability throughout thepolymer.

The products and processes of this invention also apply to various typesof polymeric materials, for example, any polypropylene, any polyamide,any polyether ketone, or any polyolefin, includinghigh-density-polyethylene, low-density-polyethylene,linear-low-density-polyethylene, ultra-high molecular weightpolyethylene (UHMWPE), copolymers or mixtures thereof. The products andprocesses of this invention also apply to various types of hydrogels,for example, poly(vinyl alcohol), poly(ethylene glycol), poly(ethyleneoxide), poly(acrylic acid), poly(methacrylic acid), poly(acrylamide),copolymers or mixtures thereof, or copolymers or mixtures of these withany polyolefin. Polymeric materials, as used herein, also applies topolyethylene of various forms, for example, resin, powder, flakes,particles, powder, or a mixture thereof, or a consolidated form derivedfrom any of the above. Polymeric materials, as used herein, also appliesto hydrogels of various forms, for example, film, extrudate, flakes,particles, powder, or a mixture thereof, or a consolidated form derivedfrom any of the above.

Blending of additives in the polymeric material resin can be done by:(i) dissolving one or more additive in a solvent or a mixture ofsolvents, (ii) mixing the polymer resin with the additive solution, and(iii) drying the solvent(s) by evaporation, optionally using elevatedtemperature or vacuum.

Solvents can be chosen from organic solvents such as acetic acid,acetone, acetonitrile, benzene, butanols, butanone, carbontetrachloride, chlorobenzene, chloroform, cyclohexane,1,2-dicholoethane, diethyl ether, diethylene glycol, diethylene glycoldiethyl ether, 1,2-dimethoxyethane, dimethyl ether, dimethylformamide,dimethyl sulfoxide, dioxane, ethanol, ethyl acetate, ethylene glycol,glycerin, heptane, hexane, methanol, pentane, propanols, pyridine,tetrahydrofuran, toluene, xylene or they can be aqueous solvents.Aqueous solvents can be pure water or solution of other compounds suchas acids, salts, or bases in water. They can be aqueous solutions ofsurfactants (generally amphiphilic compounds) such as fatty acids. Theycan also be inorganic non-aqueous solvents such as liquid alumina. Thesolvent can also be a supercritical fluid such as supercritical carbondioxide.

The solvent is typically selected depending on the solubility of theadditives desired to be blended into the polymer. The polymer resin canoptionally dissolve in the same solvent. Different additives can bedissolved in different solvents and mixed together before mixing in thepolymer or can be separately mixed with the polymer powder. In each casemore than one solvent can be used. Dissolution of the additives can beenhanced or enabled by raising the temperature or pressure or raisingthe temperature and pressure such that the solvent is in thesupercritical state.

The terms “about” or “approximately” in the context of numerical valuesand ranges refers to values or ranges that approximate or are close tothe recited values or ranges such that the invention can perform asintended, such as utilizing a method parameter (e.g., time, dose, doserate/level, and temperature), having a desired degree of cross-linkingand/or a desired lack of or quenching of free radicals, as is apparentto the skilled person from the teachings contained herein. This is due,at least in part, to the varying properties of polymer compositions.Thus, these terms encompass values beyond those resulting fromsystematic error. These terms make explicit what is implicit, as knownto the person skilled in the art.

The term ‘extraction’ refers to the removal of one or more componentsfrom the polymeric material. It can refer to the removal of anantioxidant from the surface of an antioxidant-blended polymericmaterial in powder, resin, flake form or in consolidated form.

The term ‘surface’ refers to region in the implant which is highlycross-linked after irradiation. Since, amount of cross-linking willdepend on the concentration of antioxidant before irradiation, we candefine surface in terms of FTIR index of antioxidant (or concentration)before irradiation. For example, ‘surface’ for vitamin E is defined asregion in the implant where FTIR index is below 0.04.

‘Bulk’ is defined as a region with low cross-linking potential. Since,amount of cross-linking will depend on the concentration ofanti-cross-linking agent or antioxidant before irradiation, we candefine surface in terms of FTIR index of antioxidant (or concentration)before irradiation. For example, ‘bulk’ for vitamin E is defined asregion in the implant where FTIR index is above 0.16 (approximately 1 wt%).

The term ‘backside surface’ is defined as the surface(s) or region(s) ofa joint implant, which would be intended to be in contact with theinside of an acetabular shell, a tibial plate or in direct contact withthe bone. It generally means the opposite side of the implant from thearticular surface in contact with the joint space. Not all of thebackside surface needs to be in contact with the shell, plate or bone orany other opposing surface. Sometimes, the backside surface can be alsoan articular surface, intended in the design of the implant orunintended because of loosening.

The term ‘annealing below melt’ refers to heating a polymer material toany temperature below ‘melting point’ and cooling down slowly down toroom temperature.

The term ‘melt annealing’ refers to heating a polymer material to anytemperature above ‘melting point’ and cooling down slowly to roomtemperature.

The term ‘melting point’ or ‘melt’ refers to the peak meltingtemperature of the polymeric material measured by a differentialscanning calorimeter at a heating rate of 10° C. per minute when heatingfrom −20° C. to 200° C. There may be melting of part of the polymericmaterial at temperatures below this temperature.

The term ‘consolidation’ refers generally to processes used to convertthe polymeric material resin, particles, flakes, i.e. small pieces ofpolymeric material into a mechanically integral large-scale solid form,which can be further processed, by for example machining in obtainingarticles of use such as medical implants. Methods such as injectionmolding, extrusion, compression molding, iso-static pressing (hot orcold), etc. can be used.

In the case of UHMWPE, consolidation is most often performed by“compression molding”. In some instances consolidation can beinterchangeably used with compression molding. The molding processgenerally involves: (i) heating the polymeric material to be molded,(ii) pressurizing the polymeric material while heated, (iii) maintainingthe polymeric material at the temperature and pressure, and (iv) coolingdown and releasing pressure.

Heating of the polymeric material can be done at any rate. Temperaturecan be increased linearly with time or in a step-wise fashion or at anyother rate. Alternatively, the polymeric material can be placed in apre-heated environment. The mold for the consolidation can be heatedtogether or separately from the polymeric material to be molded. Steps(i) and (ii), i.e. heating and pressurizing before consolidation can bedone in multiple steps and in any order. For example, a polymericmaterial can be pressurized at room temperature to a set pressure level1, after which it can be heated and pressurized to another pressurelevel 2, which still may be different from the pressure or pressure(s)in step (iii). Step (iii), where a high temperature and pressure aremaintained is the ‘dwell period’ where a major part of the consolidationtakes place. One temperature and pressure or several temperatures andpressures can be used during this time without releasing pressure at anypoint. For example, dwell temperatures in the range of 135° C. to 350°C. and dwell pressures in the range of 0.1 MPa to 100 MPa or up to 1000MPa can be used. The dwell time can be from 1 minute to 24 hours, morepreferably from 2 minutes to 1 hour, most preferably about 10 minutes.The temperature(s) at step (iii) are termed ‘dwell’ or ‘molding’temperature(s). The pressure(s) used in step (iii) are termed ‘dwell’ or‘molding’ pressure(s). The order of cooling and pressure release (stepiv) can be used interchangeably. In some embodiments, the cooling andpressure release may follow varying rates independent of each other.

In some embodiments, the consolidated polymeric material is fabricatedthrough “direct compression molding” (DCM), which is compression moldingusing parallel plates or any plate/mold geometry which can directlyresult in an implant or implant preform. Preforms are generallyoversized versions of implants, where some machining of the preform cangive the final implant shape.

Compression molding can also be done such that the polymeric material isdirectly compression molded onto a second surface, for example a metalor a porous metal to result in an implant or implant preform. This typeof molding results in a “hybrid interlocked polymeric material” or“hybrid interlocked medical implant preform” or “hybrid interlockedmedical implant”. Molding is conducted with a metal piece that becomesan integral part of the consolidated polymeric article. For example, acombination of antioxidant-containing polyethylene resin, powder, orflake and virgin polyethylene resin, powder or flake is directcompression molded into a metallic acetabular cup or a tibial baseplate. The porous tibial metal base plate is placed in the mold,antioxidant blended polymeric resin, powder, or flake is added on top.Prior to consolidation, the pores of the metal piece can be filled witha waxy or plaster substance through half the thickness to achievepolyethylene interlocking through the other unfilled half of themetallic piece. The pore filler is maintained through the processing andirradiation to prevent infusion of components in to the pores of themetal. In some embodiments, the article is machined after processing toshape an implant. Alternatively, in some embodiments, the porous metalcan be used as an external doping source where it is filled withadditive such as antioxidant(s) during high temperature exposure afterconsolidation into the hybrid interlocked medical implant preform. Insome embodiments, there is more than one metal piece integral to thepolymeric article. The metal(s) may be porous only in part ornon-porous. In another embodiment, one or some or all of the metalpieces integral to the polymeric article is a porous metal piece thatallows bone in-growth when implanted into the human body. In oneembodiment, the porous metal of the implant is sealed using a sealant toprevent or reduce the infusion of additive/antioxidant (in diffusionsteps after consolidation) into the pores during the selective doping ofthe implant. Preferably, the sealant is water soluble. But othersealants are also used. The final cleaning step that the implant issubjected to also removes the sealant. Alternatively, an additionalsealant removal step is used. Such sealants as water, saline, aqueoussolutions of water soluble polymers such as poly-vinyl alcohol, watersoluble waxes, plaster of Paris, or others are used. In addition, aphotoresist like SU-8, or other, may be cured within the pores of theporous metal component. Following processing, the sealant may be removedvia an acid etch or a plasma etch.

Compression molding can also be done by “layered molding”. This refersto consolidating a polymeric material by compression molding one or moreof its resin forms, which may be in the form of flakes, powder, pelletsor the like or consolidated forms in layers such that there are distinctregions in the consolidated form containing different concentrations ofadditives such as antioxidant(s). Whenever a layered-molded polymericmaterial is described in the examples below and is used in any of theembodiments it can be fabricated by:

layered molding of polymeric resin powder or its additive blends whereone or more layers contain additive and one or more layers contain oneor more additives, or antioxidants of different or identicalconcentrations;

molding together of previously molded layers of polymeric materialcontaining different or identical concentration of additives such asantioxidant(s); or

molding of UHMWPE resin powder with or without additive on to a at leastone previously molded polymeric material with or without additive.

The layer or layers to be molded can be heated in liquid(s), in water,in air, in inert gas, in supercritical fluid(s) or in any environmentcontaining a mixture of gases, liquids or supercritical fluids beforepressurization. The layer or layers can be pressurized individually atroom temperature or at an elevated temperature below the melting pointor above the melting point before being molded together. The temperatureat which the layer or layers are pre-heated can be the same or differentfrom the molding or dwell temperature(s). The temperature can begradually increased from pre-heat to mold temperature with or withoutpressure. The pressure to which the layers are exposed before moldingcan be gradually increased or increased and maintained at the samelevel.

During molding, different regions of the mold can be heated to differenttemperatures. The temperature and pressure can be maintained duringmolding for 1 second up to 1000 hours or longer. During cool-down underpressure, the pressure can be maintained at the molding pressure orincreased or decreased. The cooling rate can be 0.0001° C./minute to120° C./minute or higher. The cooling rate can be different fordifferent regions of the mold. After cooling down to about roomtemperature, the mold can be kept under pressure for 1 second to 1000hours. Or the pressure can be released partially or completely at anelevated temperature.

The term ‘heating’ refers to the thermal treatment of the polymer at orto a desired heating temperature. In one aspect, heating can be carriedout at a rate of about 10° C. per minute to the desired heatingtemperature. In another aspect, the heating can be carried out at thedesired heating temperature for a desired period of time. In otherwords, heated polymers can be continued to heat at the desiredtemperature, below or above the melting point, for a desired period oftime. Heating time at or to a desired heating temperature can be atleast 1 minute to 48 hours to several weeks long. In one aspect theheating time is about 1 hour to about 24 hours. In another aspect, theheating can be carried out for any time period as set forth herein,before or after irradiation. Heating temperature refers to the thermalcondition for heating in accordance with the invention. Heating can beperformed at any time in a process, including during, before and/orafter irradiation. Heating can be done with a heating element. Othersources of energy include the environment and irradiation.

The term “high temperature exposure” refers to thermal treatment of thepolymer or a starting material to a temperature between about 200° C.and about 500° C. or more, for example, temperature of about 200° C.,about 250° C., about 280° C., about 300° C., about 320° C., about 350°C., about 380° C., about 400° C., about 420° C., about 450° C., about480° C. or more. Heating time at “high temperature melting” can be atleast 30 minutes to 48 hours to several weeks long. In one aspect the“high temperature melting” time is continued for about 1 minute to about48 hours or more. For example, the heating is continued for at least forone minute, 10 minutes, 20 minutes, 30 minutes, one hour, two hours,five hours, ten hours, 24 hours, or more.

The term “annealing” refers to heating or a thermal treatment conditionof the polymers in accordance with the invention. Annealing generallyrefers to continued heating of the polymers at a desired temperaturebelow its peak melting point for a desired period of time, but in theinvention refers to the thermal treatment of polymeric material at anydesired temperature for a period of time. Annealing time can be at least1 minute to several weeks long. In one aspect the annealing time isabout 4 hours to about 48 hours, preferably 24 to 48 hours and morepreferably about 24 hours. “Annealing temperature” refers to the thermalcondition for annealing in accordance with the invention.

The term “packaging” refers to the container or containers in which amedical device is packaged and/or shipped. Packaging can include severallevels of materials, including bags, blister packs, heat-shrinkpackaging, boxes, ampoules, bottles, tubes, trays, or the like or acombination thereof. A single component may be shipped in severalindividual types of package, for example, the component can be placed ina bag, which in turn is placed in a tray, which in turn is placed in abox. The whole assembly can be sterilized and shipped. The packagingmaterials include, but are not limited to, vegetable parchments,multi-layer polyethylene, Nylon 6, polyethylene terephthalate (PET), andpolyvinyl chloride-vinyl acetate copolymer films, polypropylene,polystyrene, and ethylene-vinyl acetate (EVA) copolymers.

The term ‘sterile’ refers to what is known in the art; to a condition ofan object that is sufficiently free of biological contaminants and issufficiently sterile to be medically acceptable, i.e., will not cause aninfection or require revision surgery.

The term ‘cross-linking’ refers to what is known in the art as aprocessing method for polymeric materials comprising the chemicallylinking of parts of the polymeric material. Polymeric materials, forexample, UHMWPE, can be cross-linked by a variety of approaches,including those employing cross-linking chemicals (such as peroxidesand/or silane) and/or irradiation. Cross-linked UHMWPE can be obtainedaccording to the teachings of U.S. Pat. No. 5,879,400, PCT/US99/16070,filed on Jul. 16, 1999, PCT/US97/02220, filed Feb. 11, 1997, U.S. PatentApplication Publication No. 2003/0149125 (U.S. application Ser. No.10/252,582), filed Sep. 24, 2002, and U.S. Pat. No. 6,641,617.

The term ‘substantial cross-linking’ refers to the state of a polymericmaterial with a cross-link density of 30 mol/m³. The cross-link densityis measured by swelling a roughly 3×3×3 mm cube of polymeric material inxylene. The samples are weighed before swelling in xylene at 130° C. for2 hours and they are weighed immediately after swelling in xylene. Theamount of xylene uptake is determined gravimetrically, then converted tovolumetric uptake by dividing by the density of xylene; 0.75 g/cm³. Byassuming the density of polyethylene to be approximately 0.94 g/cm³, thevolumetric swell ratio of cross-linked UHMWPE was then determined. Thecross-link density is calculated using the swell ratio as described inOral et al., Biomaterials 31: 7051-7060 (2010) and is reported inmol/m³. Thus, a substantially cross-linked polymeric material has across-link density of about 30 mol/m³ in at least one part of thepolymeric material. The term ‘highly cross-linked’ refers to the stateof a polymeric material with a cross-link density of about 100 mol/m³ inat least one part of the polymeric material. For example, an implantwith surfaces having a cross-link density of about 250 mol/m³, and thebulk regions having a cross-link density of about 60 mol/m³ would behighly cross-linked.

The term ‘antioxidant’ refers to additives that protect the host polymeragainst oxidation under various aggressive environments, such as duringhigh temperature consolidation, high temperature cross-linking, lowtemperature cross-linking, irradiation, etc. Antioxidants/free radicalscavengers/anti-cross-linking agents can be chosen from but not limitedto glutathione, lipoic acid, vitamins such as ascorbic acid (vitamin C),vitamin B, vitamin D, vitamin E, tocopherols (synthetic or natural,alpha-, gamma-, delta-), acetate vitamin esters, water solubletocopherol derivatives, tocotrienols, water soluble tocotrienolderivatives; melatonin, carotenoids including various carotenes, lutein,pycnogenol, glycosides, trehalose, polyphenols and flavonoids,quercetin, lycopene, lutein, selenium, nitric oxide, curcuminoids,2-hydroxytetronic acid; cannabinoids, synthetic antioxidants such astertiary butyl hydroquinone, 6-amino-3-pyrodinoles, butylatedhydroxyanisole, butylated hydroxytoluene, ethoxyquin, tannins, propylgallate, other gallates, Aquanox family; Irganox® and Irganox® Bfamilies including Irganox® 1010, Irganox® 1076, Irganox® 1330, Irganox®1035; Irgafos® family; phenolic compounds with different chain lengths,and different number of OH groups; enzymes with antioxidant propertiessuch as superoxide dismutase, herbal or plant extracts with antioxidantproperties such as St. John's Wort, green tea extract, grape seedextract, rosemary, oregano extract, mixtures, derivatives, analogues orconjugated forms of these. They can be primary antioxidants withreactive OH or NH groups such as hindered phenols or secondary aromaticamines, they can be secondary antioxidants such as organophosphoruscompounds or thiosynergists, they can be multifunctional antioxidants,hydroxylamines, or carbon centered radical scavengers such as lactonesor acrylated bis-phenols. The antioxidants can be selected individuallyor used in any combination. Also, antioxidants can be used with inconjunction with other additives such as hydroperoxide decomposers.

Irganox®, as described herein refers to a family of antioxidantsmanufactured by Ciba Specialty Chemicals. Different antioxidants aregiven numbers following the Irganox® name, such as Irganox® 1010,Irganox® 1035, Irganox® 1076, Irganox® 1098, etc. Irgafos® refers to afamily of processing stabilizers manufactured by Ciba SpecialtyChemicals. Irganox® family has been expanded to include blends ofdifferent antioxidants with each other and with stabilizers fromdifferent families such as the Irgafos® family. These have been givendifferent initials after the Irganox® name, for instance, the Irganox®HP family are synergistic combinations of phenolic antioxidants,secondary phosphate stabilizers and the lactone Irganox® HP-136.Similarly, there are Irganox® B (blends), Irganox® L (aminic), Irganox®E (with vitamin E), Irganox® ML, Irganox® MD families. Herein we discussthese antioxidants and stabilizers by their tradenames, but otherchemicals with equivalent chemical structure and activity can be used.Addition, these chemicals can be used individually or in mixtures of anycomposition.

Polymeric material: “Polymeric materials” or “polymer” generally refersto what is known in the art as a macromolecule composed of chemicallybonded repeating structural subunits. Polymeric materials includepolyethylene, for example, ultrahigh molecular weight polyethylene(UHMWPE). Ultra-high molecular weight polyethylene (UHMWPE) refers tolinear substantially non-branched chains of ethylene having molecularweights in excess of about 500,000, preferably above about 1,000,000,and more preferably above about 2,000,000. Often the molecular weightscan reach about 8,000,000 or more. By initial average molecular weightis meant the average molecular weight of the UHMWPE starting material,prior to any irradiation. See U.S. Pat. No. 5,879,400, PCT/US99/16070,filed on Jul. 16, 1999, and PCT/US97/02220, filed Feb. 11, 1997. Theterm “polyethylene article” or “polymeric article” or “polymer”generally refers to articles comprising any “polymeric material”disclosed herein.

“Polymeric materials” or “polymers” can also include structural subunitsdifferent from each other. Such polymers can be di- or tri- or multipleunit-copolymers, alternating copolymers, star copolymers, brushpolymers, grafted copolymers or interpenetrating polymers. They can beessentially solvent-free during processing and use such asthermoplastics or can include a large amount of solvent such ashydrogels. Polymeric materials also include synthetic polymers, naturalpolymers, blends and mixtures thereof. Polymeric materials also includedegradable and non-degradable polymers.

“Polymeric materials” or “polymer” also include such as poly(vinylalcohol), poly(acrylamide), poly(acrylic acid), poly(ethylene glycol),poly(ethylene oxide), blends thereof, or interpenetrating networksthereof, which can absorb water such that water constitutes at least 1to 10,000% of their original weight, typically 100 wt % of theiroriginal weight or 99% or less of their weight after equilibration inwater.

“Polymeric material” or “polymer” can be in the form of resin, flakes,powder, consolidated stock, implant, and can contain additives such asantioxidant(s). The “polymeric material” or “polymer” also can be ablend of one or more of different resin, flakes or powder containingdifferent concentrations of an additive such as an antioxidant. Theblending of resin, flakes or powder can be achieved by the blendingtechniques known in the art. The “polymeric material” also can be aconsolidated stock of these blends.

‘Blending’ generally refers to mixing of a polymeric material in itspre-consolidated form with an additive. If both constituents are solid,blending can be done by using other component(s) such as a liquid tomediate the mixing of the two components, after which the liquid isremoved by evaporating. If the additive is liquid, for example,α-tocopherol, then the polymeric material can be mixed with largequantities of liquid. This high concentration blend can be diluted downto desired concentrations with the addition of lower concentrationblends or virgin polymeric material without the additive to obtain thedesired concentration blend. This technique also results in improveduniformity of the distribution of the additive in the polymericmaterial. In the case where an additive is also an antioxidant, forexample vitamin E, or α-tocopherol, then blended polymeric material isalso antioxidant-doped. Polymeric material, as used herein, also appliesto blends of a polyolefin and a cross-linking agent, for example a blendof UHMWPE resin powder blended with peroxide(s) and consolidated.Polymeric material, as used herein, also applies to blends ofantioxidant (s), polyolefin(s) and cross-linking agent(s).

The products and processes of this invention also apply to various typesof polymeric materials, for example, any polypropylene, any polyamide,any polyether ketone, or any polyolefin, includinghigh-density-polyethylene, low-density-polyethylene,linear-low-density-polyethylene, ultra-high molecular weightpolyethylene (UHMWPE), copolymers or mixtures thereof. The products andprocesses of this invention also apply to various types ofhydrogel-forming polymers, for example, poly(vinyl alcohol), poly(vinylacetate), poly(ethylene glycol), poly(ethylene oxide), poly(acrylicacid), poly(methacrylic acid), poly(acrylamide), copolymers or mixturesthereof, or copolymers or mixtures of these with any polyolefin.Polymeric materials, as used herein, also applies to polyethylene ofvarious forms, for example, resin, powder, flakes, particles, powder, ora mixture thereof, or a consolidated form derived from any of the above.Polymeric materials, as used herein, also applies to hydrogels ofvarious forms, for example, film, extrudate, flakes, particles, powder,or a mixture thereof, or a consolidated form derived from any of theabove.

The term “additive” refers to any material that can be added to a basepolymer in less than 50 v/v %. This material can be an organic orinorganic material with a molecular weight less than that of the basepolymer. An additive can impart different properties to the polymericmaterial, for example, it can be a cross-linking agent or anantioxidant.

The term “non-permanent device” refers to what is known in the art as adevice that is intended for implantation in the body for a period oftime shorter than several months. Some non-permanent devices could be inthe body for a few seconds to several minutes, while other may beimplanted for days, weeks, or up to several months. Non-permanentdevices include catheters, tubing, intravenous tubing, and sutures, forexample. The term “permanent device” refers to what is known in the artthat is intended for implantation in the body for a period longer thanseveral months. Permanent devices include medical devices, for example,acetabular liner, shoulder glenoid, patellar component, finger jointcomponent, ankle joint component, elbow joint component, wrist jointcomponent, toe joint component, bipolar hip replacements, tibial kneeinsert, tibial knee inserts with reinforcing metallic and polyethyleneposts, intervertebral discs, sutures, tendons, heart valves, stents, andvascular grafts. The term “medical implant” refers to what is known inthe art as a device intended for implantation in animals or humans forshort or long term use. The medical implants, according to an aspect ofthe invention, comprises medical devices including acetabular liner,shoulder glenoid, patellar component, finger joint component, anklejoint component, elbow joint component, wrist joint component, toe jointcomponent, bipolar hip replacements, tibial knee insert, tibial kneeinserts with reinforcing metallic and polyethylene posts, intervertebraldiscs, sutures, tendons, heart valves, stents, vascular grafts.

The term “packaging” refers to the container or containers in which amedical device is packaged and/or shipped. Packaging can include severallevels of materials, including bags, blister packs, heat-shrinkpackaging, boxes, ampoules, bottles, tubes, trays, or the like or acombination thereof. A single component may be shipped in severalindividual types of package, for example, the component can be placed ina bag, which in turn is placed in a tray, which in turn is placed in abox. The whole assembly can be sterilized and shipped. The packagingmaterials include, but are not limited to, vegetable parchments,multi-layer polyethylene, Nylon 6, polyethylene terephthalate (PET), andpolyvinyl chloride-vinyl acetate copolymer films, polypropylene,polystyrene, and ethylene-vinyl acetate (EVA) copolymers.

The term “annealing” refers to heating or a thermal treatment conditionof the polymers in accordance with the invention. Annealing generallyrefers to continued heating of the polymers at a desired temperaturebelow its peak melting point for a desired period of time, but in theinvention refers to the thermal treatment of polymeric material at anydesired temperature for a period of time. Annealing time can be at least1 minute to several weeks long. In one aspect the annealing time isabout 4 hours to about 48 hours, preferably 24 to 48 hours and morepreferably about 24 hours. “Annealing temperature” refers to the thermalcondition for annealing in accordance with the invention.

The term ‘heating’ refers to the thermal treatment of the polymer at orto a desired heating temperature. In one aspect, heating can be carriedout at a rate of about 10° C. per minute to the desired heatingtemperature. In another aspect, the heating can be carried out at thedesired heating temperature for a desired period of time. In otherwords, heated polymers can be continued to heat at the desiredtemperature, below or above the melting point, for a desired period oftime. Heating time at or to a desired heating temperature can be atleast 1 minute to 48 hours to several weeks long. In one aspect theheating time is about 1 hour to about 24 hours. In another aspect, theheating can be carried out for any time period as set forth herein,before or after irradiation. Heating temperature refers to the thermalcondition for heating in accordance with the invention. Heating can beperformed at any time in a process, including during, before and/orafter irradiation. Heating can be done with a heating element. Othersources of energy include the environment and irradiation.

The term ‘sterile’ refers to what is known in the art; to a condition ofan object that is sufficiently free of biological contaminants and issufficiently sterile to be medically acceptable, i.e., will not cause aninfection or require revision surgery.

Cross-linking: Polymeric Materials, for example, UHMWPE can becross-linked by a variety of approaches, including those employingcross-linking chemicals (such as peroxides and/or silane) and/orirradiation. Cross-linked UHMWPE can be obtained according to theteachings of U.S. Pat. No. 5,879,400, PCT/US99/16070, filed on Jul. 16,1999, PCT/US97/02220, filed Feb. 11, 1997, U.S. Patent ApplicationPublication No. 2003/0149125 (U.S. application Ser. No. 10/252,582),filed Sep. 24, 2002, and U.S. Pat. No. 6,641,617, the entirety of whichare hereby incorporated by reference.

The term ‘masking’ refers to covering of one or more surface(s) orregions within surface(s) during any of the processes described herein.Generally, masking involves bringing the polymeric material, medicalimplant preform or medical implant in contact with a masking material.Masking area could be anywhere from 0% to 99% of the total surface areaof any of the surface(s). Parts of the same surface, for examplearticular surface, can be masked. In any of the embodiments, materialused for masking could be any material whose dimensional change uponheating for high temperature exposure is small. Preferably, the maskingmaterial does not melt below or at the temperature used during hightemperature exposure. If the masking material melts, it preferably doesnot exude or leach any parts into the polymeric material being masked.Examples of such materials can be metals such as aluminum, copper, ironor any other material which fits this description. The masking materialcan be of any practically feasible thickness, from 1 microns to 1 meter,preferably 100 microns to 500 microns. Masking materials can becontinuous or multiple masks of different materials and shapes andthicknesses can be used simultaneously. For example, medical implantpreforms can be seated on a metal bar with conforming surfaces andsimultaneously several masks can be used to cover parts of the rim andlocking mechanisms while being exposed to high temperature. Depending onthe thickness and material used, masks can be flexible, pliable orrigid.

The term “toughness” of a material refers to its ability to distributean applied stress such that failure does not occur until there are veryhigh stresses. It is quantified by the area under the stress-straincurve of a material. For example, a higher work-to-failure, which is thearea under the engineering stress-strain curve obtained from tensilemechanical testing, is attributed directly to increased toughness. Forexample, toughness also refers to impact toughness, which is thework-to-failure as measured by impact testing. In the examples, this isdemonstrated by IZOD impact testing according to ASTM F648.

The term ‘fatigue strength’ refers to the resistance of a material tocrack formation under cyclic stresses for a prolonged period of timeunder stress levels lower than its yield strength. It is oftencharacterized by fatigue crack propagation resistance as described, forexample in ASTM E647.

The term “doping” refers to a process known in the art (see, forexample, U.S. Pat. Nos. 6,448,315 and 5,827,904). In this connection,doping generally refers to contacting a polymeric material with acomponent or the solution/emulsion of a component under certainconditions, as set forth herein, for example, doping UHMWPE with anantioxidant under supercritical conditions. “Doping” also refers tointroducing additive into the base polymeric material in quantities lessthan 50 v/v %. A polymeric material treated in such a way for example toincorporate an antioxidant is termed as an “antioxidant-doped” polymericmaterial. The polymeric material can be ‘doped’ by other additives aswell, such as a cross-linking agent, in which case the polymericmaterial treated in such a way may be termed as ‘cross-linkingagent-doped’.

Doping may also be done by diffusing an additive into the polymericmaterial by immersing the polymeric material, by contacting thepolymeric material with the additive in the solid state, or with a bathof the additive in the liquid state, or with a mixture of the additivein one or more solvents in solution, emulsion, suspension, slurry,aerosol form or in a gas or in a supercritical fluid. The doping processby diffusion can involve contacting a polymeric material, medicalimplant or device with an additive, such as vitamin E, for about an hourup to several days, preferably for about one hour to 24 hours, morepreferably for one hour to 16 hours. The environment for the diffusionof the additive (bath, solution, emulsion, paste, slurry and the like)can be heated to room temperature or up to about 200° C. and the dopingcan be carried out at room temperature or up to about 200° C.Preferably, the antioxidant can be heated to 100° C. and the doping iscarried out at 100° C. A polymeric material incorporated with anadditive by diffusion in such a way is termed an ‘additive-diffused’polymeric material. For example, a polymeric material immersed in a bathof antioxidant(s) for enough time to dope at least some parts of thepolymeric material with the antioxidant(s), is termed an‘antioxidant-doped’ or ‘antioxidant-diffused’ polymeric material.

To increase the depth of diffusion of the antioxidant, the material canbe doped for longer durations, at higher temperatures, at higherpressures, and/or in presence of a supercritical fluid.

The doped polymeric material can be annealed by heating below or abovethe melting point of the polymeric material subsequent to doping. Theannealing is preferably for about an hour up to several days, morepreferably for about one hour to 24 hours, most preferably for one hourto 16 hours. The doped polymeric material can be heated to roomtemperature or up to about 350° C. and the annealing can be carried outat room temperature or up to about 350° C. Preferably, the dopedpolymeric material can be heated to 120° C. and the annealing is carriedout at 120° C. Annealing can be performed in liquid(s), in air, in othergases such as oxygen, in inert gas, in supercritical fluid(s), or invacuum. Annealing can also be performed in ambient pressure, aboveambient pressure or below ambient pressure. Annealing can also beperformed while the polymeric material is immersed in liquidantioxidant, such as vitamin E, or a solution/emulsion ofantioxidant(s).

By “crystallinity” is meant the fraction of the polymer that iscrystalline. The crystallinity is calculated by knowing the weight ofthe sample (w, in grams), the heat absorbed by the sample in melting (E,in J/g) and the heat of melting of polyethylene crystals (ΔH=291 J/g),and using Equation 1 according to ASTM F2625 and the like or theirsuccessors:

$\begin{matrix}{{\% \mspace{14mu} {Crystallinity}} = {\frac{E}{w} \times \Delta \; H}} & \left( {{Eq}.\mspace{14mu} 1} \right)\end{matrix}$

The invention is further illustrated in the following Examples which arepresented for purposes of illustration and not of limitation.

EXAMPLES Example 1. Surface Extraction of Vitamin E from VitaminE-Containing UHMWPE Pucks Using a Nitrogen Convection Oven

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E (Acros™99% D,L-α-tocopherol, DSM Nutritionals, NJ), then mixing the vitaminE-IPA solution with virgin UHMWPE powder, then evaporating off thesolvent in a vacuum oven at an elevated temperature (approximately 60°C.). The mixture was diluted with GUR 1050 to obtain GUR 1050 with 1 wt% vitamin E.

Two pucks (diameter 10 cm, thickness 1-1.1 cm) of the 1 wt % vitaminE-containing UHMWPE blend were prepared via compression molding. Thepowder was pre-heated in a vacuum oven under partial vacuum/inert gas at190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press (3895 Auto-M, Carver, Wabash, Ind.)where it was sintered, then compressed to 20 MPa at about 194° C. for 10minutes, then cooled to room temperature under pressure. Then, the puckwas cooled in approximately 1.5 hours under pressure.

Two pucks were placed on top of each other (to obtain a sample withdouble the effective diffusion distance from the surface) and maskedwith aluminum foil from 5 sides except one circular surface. They wereplaced in a pre-heated nitrogen convection oven at 290° C. with theunmasked surface exposed to nitrogen flow. The pucks were kept in theoven under these conditions for approximately 290 minutes. Samples wereremoved from the oven and were cooled in air at room temperature.

The sample was removed from the oven and cut at a distance far from theside walls near the center (FIG. 1) and the cut surface was microtomedto get a thin 150 micron film for Fourier Transform InfraredSpectroscopy (FTIR) analysis of vitamin E index. Spectra were collectedin transmission with a resolution of 4 cm⁻¹ with an average of 32 scans.A vitamin E index was calculated by normalizing the area of the peak at1260 cm⁻¹ (from 1226 cm⁻¹ to 1295 cm⁻¹) to the peak at 1895 cm⁻¹ (1850cm⁻¹ to 1985 cm⁻¹). Vitamin E index plotted against depth of the sampleis presented in FIG. 2. Here x=0 refers to the exposed surface availablefor extraction while x=20 refers to the masked surface in contact withthe bottom surface of oven. Results are only presented for first 10 mmof the sample. The vitamin E index at and close to the surface wasdecreased, thereby creating a UHMWPE with a gradient in vitamin Econcentration.

Example 2. Radiation Cross-Linking of a Surface Extracted UHMWPEContaining Vitamin E

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E, thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 0.75 wt % vitamin E.

Two pucks (diameter 10 cm, thickness 1-1.1 cm) of the 0.75 wt % vitaminE-containing UHMWPE blend were prepared via compression molding. Thepowder was pre-heated in a vacuum oven under partial vacuum/inert gas at190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press (3895 Auto-M, Carver, Wabash, Ind.)where it was sintered, then compressed to 20 MPa at about 194° C. for 10minutes, then cooled to room temperature under pressure. Then, the puckwas cooled in approximately 1.5 hours under pressure.

Two pucks were placed on top of each other (to obtain a sample withdouble the effective diffusion distance from the surface) and maskedwith aluminum foil from 5 sides except one circular surface. They wereplaced in a pre-heated nitrogen convection oven at 290° C. with theunmasked surface exposed to nitrogen flow. The pucks were kept in theoven under these conditions for approximately 3.5 hours. Samples wereremoved from the oven and were cooled in air at room temperature.

After cooling down, the top puck was irradiated by electron beamirradiation using a Van-de-Graff generator at 3.0 MeV to a dose of 175kGy at 25 kGy/pass.

The vitamin E index as a function of depth is shown before and afterirradiation in FIG. 3. The vitamin E index was decreased afterirradiation and the vitamin E index at x=2 mm was below 0.04.

The cross-link density of sections from the irradiated pucks wascalculated. Samples (3×3×1 mm) were cut by razor blade as shown in FIG.4. Samples were obtained at an approximate depth of 1.5 mm and 8.5 mmrespectively from the extracted surface. The samples were swollen inxylene pre-heated to 130° C. for 2 hours. Weights of sample weremeasured before and after xylene swelling.

Cross-link density was calculated using Equation 2:

$\begin{matrix}{d_{x} = \frac{{\ln \left( {1 - q_{eq}^{- 1}} \right)} + {q_{eq}^{- 1}X\; q_{eq}^{- 2}}}{\left( {q_{eq}^{- \frac{1}{3}} - q_{eq}^{- 2}} \right)}} & \left( {{Eq}.\mspace{14mu} 2} \right)\end{matrix}$

where

$X = {0.33 + {\frac{0.55}{q_{eq}}.}}$

Volumetric equilibrium expansion ratio, q_(eq), was calculated fromweight swelling ratio using density of dry polyethylene as 0.94 g cm⁻³and that of xylene as 0.75 g cm⁻³ at 130° C. The control was a virginUHMWPE puck (diameter 10 cm, thickness 1.1 cm) prepared as describedabove and irradiated to 25 kGy. Cross-link density measurements weredone for virgin material by extracting samples (3×3×1 mm) atapproximately 1.5 mm and 8.5 mm from the exposed surface. Comparison ofcross-link density at surface (1.5 mm) for virgin (80±10 mol/m³) andsurface extracted (210±10 mol/m³) samples shows that the values muchhigher than conventional material.

Example 3. Optimal Wear Resistance at the Surface

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E, thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtaina vitamin E-blended GUR 1050 resin powder with 1 wt % vitamin E.

Two pucks (diameter 10 cm, thickness 1-1.1 cm) of the 1 wt % vitaminE-containing UHMWPE blend were prepared via compression molding. Thepowder was pre-heated in a vacuum oven under partial vacuum/inert gas at190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press where it was sintered, then compressedto 20 MPa at about 194° C. for 10 minutes, then cooled to roomtemperature under pressure. Then, the puck was cooled in approximately1.5 hours under pressure.

Two pucks were placed on top of each other (to obtain a sample withdouble the effective diffusion distance from the surface) and maskedwith aluminum foil from 5 sides except one circular surface. They wereplaced in a pre-heated nitrogen convection oven at 290° C. with theunmasked surface exposed to nitrogen flow. The pucks were kept in theoven under these conditions for approximately 3.5 hours. Samples wereremoved from the oven and were cooled in air at room temperature untilsteady state is reached.

As specified earlier, cylindrical pins of 9 mm diameter and 9 mm lengthwere machined from the top 10 mm of the material by machining off 1 mmfrom the exposed surface of multidirectional pin-on-disk wear test wasconducted for the irradiated materials. Wear test was conducted for aweek (approximately 1.1 million cycles). Pins were machined off 300microns after 1 week of testing and wear rate testing was done. Similarprocedure was repeated 3 times until we have reached 1000 micron awayfrom the originally machined surface or 2 mm from the original surface.Pins were tested against CoCr in bovine serum at 2 Hz as previouslydescribed (Bragdon et al., “A new pin-on-disk wear testing method forsimulating wear of polyethylene on cobalt-chrome alloy in total hiparthroplasty”, J Arthroplasty, 2001 16(5): p. 658-65). Weight loss wasmeasured approximately every 0.125 MC and wear rate is reported as alinear regression of weight loss versus number of cycles from 0.5 MC to1 MC. Wear rate in mg/MC is plotted again depth of the material in FIG.5. A similar procedure was followed for a virgin control irradiated to25 kGy and wear rate was measured to be 8.2±1.3 mg/MC. The surface ofthe extracted sample had a much lower wear rate (p<0.01) as compared tothe conventional material (virgin, 25 kGy) even after 2 mm was machinedoff from the extracted and irradiated surface.

Example 4. Surface Extraction of Vitamin E from Vitamin E ContainingSamples Through Vacuum Oven

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E, thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainblends with 0.75 or 2 wt % vitamin E.

Two pucks (diameter 10 cm, thickness 1-1.1 cm) of the 2 wt % and 0.75 wt% vitamin E-containing UHMWPE blend were prepared via compressionmolding. The powder was pre-heated in a vacuum oven under partialvacuum/inert gas at 190-210° C. for approximately 2 hours. Then, themold/powder was transferred to an automatic press where it was sintered,then compressed to 20 MPa at about 194° C. for 10 minutes, then cooledto room temperature under pressure. Then, the puck was cooled overapproximately 1.5 hours under pressure.

Cuboids (20×10×10 mm) were cut from these pucks and were masked withaluminum foil on 5 sides and kept in a vacuum oven at 220° C. for 16hours. One 10×10 mm surface was left unexposed. Pressure in the vacuumoven was kept at 10⁻⁶ atm. Thereafter cubes were taken out from the ovenand cooled in air at room temperature until steady state was reached.Cubes were cut from the center and 150 micron sections were microtomedto be used in FTIR analysis (FIG. 1). Vitamin E index was plotted as afunction of depth in FIG. 6, where x=0 is the unmasked surface and x=20is masked surface in contact with the surface of oven. Results arepresented for the first 10 mm of the cuboid.

As evident from the plot, surface concentration of vitamin E was lowercompared to bulk concentration of vitamin E. Therefore surfaceextraction of vitamin E can be achieved by high temperature exposure andin vacuum.

Example 5. Surface Extraction of Vitamin E from Vitamin E-Containing byHigh Temperature Exposure in Air

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E, thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 1 wt % vitamin E.

A puck (diameter 10 cm, thickness 1-1.1 cm) of 1 wt % vitaminE-containing UHMWPE blend was prepared via compression molding. Thepowder was pre-heated in a vacuum oven under partial vacuum/inert gas at190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press (3895 Auto-M, Carver, Wabash, Ind.)where it was sintered, then compressed to 20 MPa at about 194° C. for 10minutes, then cooled to room temperature under pressure. Then, the puckwas cooled in approximately 1.5 hours under pressure.

Cubes machined from the puck (10 mm) were kept in an air oven on a metalmesh for 60 minutes and 105 minutes respectively. Thereafter, sampleswere cooled in air at room temperature until they reached a steadystate. FTIR analysis was done by cutting the cube from the center andmicrotoming 150 micron sections from the center (FIG. 7). Vitamin Eindex as a function of depth inside the cube is shown in FIG. 8. Herex=0 refers to one side of the cube, while x=10 refers to an opposingside of the cube. The surface concentration of vitamin E was lower thanthe bulk for both 60 minutes and 105 minutes exposure times and theamount of extraction increased as the duration increased.

Example 6. Surface Extraction of Vitamin E from Vitamin E ContainingSamples by Placing them in an Air Convection Oven at an ElevatedTemperature

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E, thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 1 wt % vitamin E.

A puck (diameter 10 cm, thickness 1-1.1 cm) of 1 wt % vitaminE-containing UHMWPE blend was prepared via compression molding. Thepowder was pre-heated in a vacuum oven under partial vacuum/inert gas at190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press where it was sintered, then compressedto 20 MPa at about 194° C. for 10 minutes, then cooled to roomtemperature under pressure. Then, the puck was cooled in approximately1.5 hours under pressure.

Two 1 cm cubes are machined from the puck and kept in an air convectionoven at 220° C. for 30 minutes and 60 minutes respectively. Thereaftercubes were taken out and cooled at room temperature until steady statewas reached. FTIR analysis was conducted on 150 micron sections thatwere microtomed from the center of the cube. The sections are parallelto the surface of the oven at x=0 refers to one side of the cube whilex=10 refers to an opposing side of the same cube (FIG. 7). Referring toFIG. 9, results are plotted as a function of depth in the sample.Vitamin E index at the surface was low compared to the bulk suggestingthat high temperature exposure in air is a viable method for extractionof vitamin E from vitamin E-blended UHMWPE.

Example 7. Manipulation of Vitamin E Profile by Changing Time inNitrogen Convection Oven

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E, thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 1 wt % vitamin E.

A puck (diameter 10 cm, thickness 1-1.1 cm) of 1 wt % vitaminE-containing UHMWPE blend was prepared via compression molding. Thepowder was pre-heated in a vacuum oven under partial vacuum/inert gas at190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press where it was sintered, then compressedto 20 MPa at about 194° C. for 10 minutes, then cooled to roomtemperature under pressure. Then, the puck was cooled over approximately1.5 hours under pressure.

Cubes (10×10×10 mm) were machined and masked with aluminum foil on 5sides and kept in a nitrogen convection oven at a temperature of 290° C.Samples were kept for different durations namely—90 minutes, 120 minutesand 210 minutes, with the exposed surface in contact with nitrogen.Thereafter, cubes were cooled in air at room temperature until steadystate was reached. FTIR analysis was carried out by cutting the cubefrom the center and scanning the surface perpendicular to the bottomsurface of the oven, similar to the method described in FIG. 1 for a 20mm cuboid. Vitamin E profile as a function of depth is plotted in FIG.10. x=0 refers to the exposed surface in contact with nitrogen, whilex=10 refers to the bottom surface, which was masked and in contact withbottom surface of oven. The amount of vitamin E extracted increased withincreasing duration of high temperature exposure. Therefore, a desiredvitamin E concentration profile could be obtained by manipulatingextraction duration.

Example 8. Manipulation of Vitamin E Profile by Changing ExtractionDuration in Vacuum Oven

As illustrated earlier, vitamin E profile and thereby wear propertiescan be manipulated by changing the duration of high temperature exposurein nitrogen. A similar set of experiments to determine the effect ofduration on concentration profile were conducted in vacuum.

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E(D,L-α-tocopherol, DSM Nutritionals, Parsipanny, N.J.), then mixing thevitamin E-IPA solution with virgin UHMWPE powder, then evaporating offthe solvent in a vacuum oven at an elevated temperature (approximately60° C.). The mixture was diluted with GUR 1050 to obtain GUR 1050 with 1wt % vitamin E.

A puck (diameter 10 cm, thickness 1-1.1 cm) of 1 wt % vitaminE-containing UHMWPE blend was prepared via compression molding. Thepowder was pre-heated in a vacuum oven under partial vacuum/inert gas at190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press where it was compressed to 20 MPa atabout 194° C. for 10 minutes, then cooled to room temperature underpressure. Then, the puck was cooled in approximately 1.5 hours underpressure.

Cubes (10 mm) were machined from 1 wt % vitamin E blended UHMWPE pucksand kept without masking on a metal mesh in a vacuum oven at 220° C. anda pressure of 2×10⁻⁶ atm (argon) for 25 minutes, 50 minutes, 105minutes, 180 minutes and 240 minutes. Cubes were removed after therespective time had elapsed and were then cooled in air at roomtemperature until steady state was reached. FTIR analysis was conductedon 150 micron sections cut from the center of the cube. Due to the factthat the cubes were unmasked, FTIR analysis was done on a surface whichwas cut from the center of the cube but was parallel to the bottom ofthe oven (FIG. 7). Results are plotted in FIG. 11, with x=0 referringone side surface of the cube and x=10 referring to the opposing sidesurface. The amount of vitamin E extracted from the surface increasedwith increasing high temperature exposure duration in vacuum; thereby adesired vitamin E profile in the sample could be obtained bymanipulating extraction duration.

Example 9. Manipulation of Vitamin E Profile by Changing Temperature inNitrogen Convection Oven

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 1 wt % vitamin E.

A puck (diameter 10 cm, thickness 1-1.1 cm) of 1 wt % vitaminE-containing UHMWPE blend was prepared via compression molding. Thepowder was pre-heated in a vacuum oven under partial vacuum/inert gas at190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press where it was sintered, then compressedto 20 MPa at about 194° C. for 10 minutes, then cooled to roomtemperature under pressure. Then, the puck was cooled over approximately1.5 hours under pressure.

Two cubes (10 mm) were machined and masked on 5 sides with aluminum foilbefore placing in a nitrogen convection oven for 90 minutes. Cubes werekept at temperatures of 180° C., 250° C. and 290° C. respectively. After90 minutes, cubes were taken out and cooled at room temperature untilsteady state was reached. FTIR analysis was performed by cutting thesample from the center and microtoming a 150 micron sectionperpendicular to the bottom surface of the oven (FIG. 7). Vitamin Eindex was plotted against depth in FIG. 12. Here x=0 represented theexposed surface to nitrogen, while x=10 mm was the masked surface whichwas kept in contact with bottom surface of oven. As the temperature wasincreased in the nitrogen convection oven, the amount of extraction ofvitamin E from the sample increased.

Example 10. Manipulation of Vitamin E Profile by Changing ExposureTemperature in Air

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 1 wt % vitamin E.

A puck (diameter 10 cm, thickness 1-1.1 cm) of 1 wt % vitaminE-containing UHMWPE blend was prepared via compression molding. Thepowder was pre-heated in a vacuum oven under partial vacuum/inert gas at190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press where it was compressed to 20 MPa atabout 194° C. for 10 minutes, then cooled to room temperature underpressure. Then, the puck was cooled in approximately 1.5 hours underpressure.

Two cubes (10×10×10 mm) were machined and placed in an air convectionoven without masking for 60 minutes at temperatures of 200° C. or 230°C. Thereafter, samples were taken out of the oven and cooled in air atroom temperature. FTIR analysis was done on cubes by cutting it from thecenter on a surface parallel to the oven (FIG. 7). Results are plottedas a function of depth in FIG. 13. Increasing temperature from 200° C.to 230° C. resulted in more extraction from the surface (2 mm.) withoutaffecting the bulk concentration of vitamin E.

Example 11. Manipulation of Vitamin E Profile by Changing InitialConcentration of Vitamin E in the Sample

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E, thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 blends with 1 or 0.75 wt % vitamin E.

Two pucks (diameter 10 cm, thickness 1-1.1 cm) of 1 wt % and 0.75 wt %vitamin E-containing UHMWPE blends were prepared via compressionmolding. The powder was pre-heated in a vacuum oven under partialvacuum/inert gas at 190-210° C. for approximately 2 hours. Then, themold/powder was transferred to an automatic press where it was sintered,then compressed to 20 MPa at about 194° C. for 10 minutes, then cooledto room temperature under pressure. Then, the puck was cooled inapproximately 1.5 hours under pressure. Cubes (10×10×10 mm) weremachined from these pucks and masked on 5 sides with aluminum foil andkept in an inert gas convection oven in nitrogen for 210 minutes.Thereafter, samples were taken out and cooled in air at room temperatureuntil steady state was reached. Cubes were cut from the center and FTIRanalysis was done on a 150 micron microtomed surface which wasperpendicular to the bottom surface of the cube. Vitamin E profile as afunction of depth in the sample is presented in FIG. 14. Here x=0 is thesurface that was exposed to nitrogen while x=10 was the masked surfacein contact with bottom surface of the oven (FIG. 1). Vitamin Econcentration profile in the sample could be manipulated by changing itsinitial concentration in the sample.

Example 12. Manipulation of Vitamin E Concentration Profile by Changingthe Masking Area

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin, thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 1 wt % vitamin E concentration.

A puck (diameter 10 cm, thickness 1-1.1 cm) of 1 wt % vitaminE-containing UHMWPE blend was prepared via compression molding. Thepowder was pre-heated in a vacuum oven under partial vacuum/inert gas at190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press where it was sintered, then compressedto 20 MPa at about 194° C. for 10 minutes, then cooled to roomtemperature under pressure. Then, the puck was cooled in approximately1.5 hours under pressure.

Two cubes (10×10×10 mm) were machined from these pucks. One of the cubeswas masked with aluminum foil on 5 sides, leaving one side exposed,while the other cube was completely unmasked. The cubes were kept on ametal mesh in a nitrogen convection oven at 290° C. for 90 minutes, withthe exposed side of the masked cube in contact with nitrogen convection.Thereafter, samples were taken out and cooled down in air at roomtemperature. The masked cube was analyzed by cutting it from the centerand FTIR analysis was performed on a 150 micron microtomed surfaceperpendicular to the bottom surface of the cube using the methoddescribed for cuboids described in FIG. 1. The unmasked cube wasanalyzed by performing FTIR analysis on a 150 micron section cut fromthe center of the cube but parallel to the bottom surface of the oven.Vitamin E profile as a function of depth in the samples is presented inFIG. 15. Here x=0 was the surface which was exposed to nitrogen whilex=10 was the masked surface in contact with bottom surface of the oven(FIG. 1). For unmasked samples, x=0 refers to one side surface of thecube and x=10 refers to the opposite side surface (FIG. 7). The resultsshowed that the vitamin E concentration profile in the sample wassignificantly different for masked and unmasked samples and that maskingprevented extraction of the vitamin E from the masked surfaces.

Example 13. Manipulation of Vitamin E Concentration Profile by CyclicHeating and Cooling

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 1 wt % vitamin E concentration.

A puck (diameter 10 cm, thickness 1-1.1 cm) of 1 wt % vitaminE-containing UHMWPE blend was prepared via compression molding. Thepowder was pre-heated in a vacuum oven under partial vacuum/inert gas at190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press where it was sintered, then compressedto 20 MPa at about 194° C. for 10 minutes, then cooled to roomtemperature under pressure. Then, the puck was cooled in approximately1.5 hours under pressure.

Two cubes (10 mm) were machined from the puck and first was kept in avacuum oven at a pressure of 2×10⁻⁶ atm (argon) and at a temperature of220° C. for 180 minutes. Thereafter, it was taken out of the oven andcooled to about room temperature. Another cube was kept in the vacuumoven at the same pressure and temperature but for 15 minutes.Thereafter, sample was taken out and cooled in water for 3 minutes. Thecomplete heating/cooling cycle was repeated 12 times for a total heatingtime of 180 minutes. FTIR analysis was conducted on 150 micron sectionsobtained from the center of the cube and parallel to the bottom surfaceof the oven (FIG. 7). Results are presented for both the cubes in FIG.16. The vitamin E concentration profile was different for these samples,which suggested that the vitamin E concentration profile could bemanipulated by conducting a cyclic heating cooling treatment as comparedto single heating cooling operation during high temperature extractionof vitamin E-blends.

Example 14. Manipulation of Vitamin E Profile by Treatment with Tween 20Surfactant after Extraction in Ovens

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E, thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 1 wt % vitamin E concentration.

A puck (diameter 10 cm, thickness 1-1.1 cm) of 1 wt % vitaminE-containing UHMWPE blend was prepared via compression molding. Thepowder was pre-heated in a vacuum oven under partial vacuum/inert gas at190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press where it was sintered, then compressedto 20 MPa at about 194° C. for 10 minutes, then cooled to roomtemperature under pressure. Then, the puck was cooled in approximately1.5 hours under pressure.

Two cubes (10×10×10 mm) were machined from the puck and were kept in avacuum oven at a pressure of 2×10⁻⁶ atm (argon) and a temperature of220° C. for 105 minutes. Thereafter, samples were taken out of the ovenand cooled in air to about room temperature. One of the cubes was boiledin Tween 20 (20% by weight in water) solution for 3 hours. FTIR analysiswas conducted on 150 micron sections obtained from the center of thecube which were parallel to the bottom surface of the oven (FIG. 7).Results are compared for both the samples in FIG. 17. The vitamin Econcentration at the surface (1 mm) of the high temperature exposed andTween 20 extracted UHMWPE was less than the high temperature exposedUHMWPE. These results showed that the vitamin E concentration profilecould be further modified by further extraction in a solution of Tween20 after extraction by high temperature exposure.

Example 15. Manipulation of Vitamin E Profile by Treatment withHexane/Ethanol after Extraction in Ovens

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E, thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 1 wt % vitamin E concentration.

A puck (diameter 10 cm, thickness 1-1.1 cm) of 1 wt % vitaminE-containing UHMWPE blend was prepared via compression molding. Thepowder was pre-heated in a vacuum oven under partial vacuum/inert gas at190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press (3895 Auto-M, Carver, Wabash, Ind.)where it was sintered, then compressed to 20 MPa at about 194° C. for 10minutes, then cooled to room temperature under pressure. Then, the puckwas cooled for approximately 1.5 hours under pressure.

Two cubes (10 mm) were machined from the puck and were kept in a vacuumoven at a pressure of 2×10⁻⁶ atm and a temperature of 220° C. for 105minutes. Thereafter, samples were taken out of the oven and cooled inair at room temperature. One of the cubes was boiled in hexane for 3hours. FTIR analysis was conducted on 150 micron sections obtained fromthe center of the cube which were parallel to the bottom surface of theoven (FIG. 7). Results are compared for both samples in FIG. 18. Thevitamin E concentration at the surface (1 mm) of the high temperatureexposed and hexane extracted UHMWPE was less than the high temperatureexposed UHMWPE. These results showed that the vitamin E concentrationprofile could be further modified by further extraction in an organicsolvent after extraction by high temperature exposure.

Example 16. Manipulation of Vitamin E Profile by Treatment with Tween 20Surfactant Before Extraction at High Temperature

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin, thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 1 wt % vitamin E concentration.

A puck (diameter 10 cm, thickness 1-1.1 cm) of 1 wt % vitaminE-containing UHMWPE blend was prepared via compression molding. Thepowder was pre-heated in a vacuum oven under partial vacuum/inert gas at190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press where it was sintered, then compressedto 20 MPa at about 194° C. for 10 minutes, then cooled to roomtemperature under pressure. Then, the puck was cooled in approximately1.5 hours under pressure.

Two cubes (10×10×10 mm) were machined from the puck and one of them wasboiled in Tween 20 solution (20 wt % in water) for 40 hours. The cubewas removed after 40 hours and both the cubes (both treated anduntreated with Tween 20) were kept in a vacuum oven at a pressure of2×10⁻⁶ atm (argon) and a temperature of 220° C. for 105 minutes.Thereafter, samples were taken out of the oven and cooled in air toabout room temperature. FTIR analysis was conducted on 150 micronsections obtained from the center of the cube which were parallel to thebottom surface of the oven (FIG. 7). Results are compared for both thesamples in FIG. 19. The vitamin E concentration of the UHMWPE blendsextracted using a Tween 20 solution followed by high temperatureexposure at 220° C. were lower in the surface and in the bulk comparedto UHMWPE blends extracted using just high temperature exposure for thesame duration at 220° C. These results showed that the vitamin Econcentration of vitamin E blends of UHMWPE could be manipulated viaextraction using a surfactant solution before high temperature exposure.

Example 17. Manipulation of Vitamin E Profile by Doing Oven Extractionon Oven Extracted and Tween 20 Treated Samples

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 1 wt % vitamin E concentration.

A puck (diameter 10 cm, thickness 1-1.1 cm) of 1 wt % vitaminE-containing UHMWPE blend was prepared via compression molding. Thepowder was pre-heated in a vacuum oven under partial vacuum/inert gas at190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press where it was sintered, then compressedto 20 MPa at about 194° C. for 10 minutes, then cooled to roomtemperature under pressure. Then, the puck was cooled in approximately1.5 hours under pressure.

Two cubes (10×10×10 mm) were machined from the puck and kept in a vacuumoven at a pressure of 2×10⁻⁶ atm (argon) and a temperature of 220° C.for 105 minutes. Thereafter, samples were taken out of the oven andcooled in air at room temperature. One of the cubes was boiled in aTween 20 solution (20 wt % in water) for 3 hours and cooled in air.Thereafter, this cube was kept in vacuum oven at 2×10⁻⁶ atm pressure(argon) and a temperature of 220° C. for 60 minutes. FTIR analysis wasconducted on 150 micron sections obtained from the center of both thecubes which were parallel to the bottom surface of the oven (FIG. 7).Results are compared for both the samples in FIG. 20. The vitamin Econcentration profile of 1 wt % vitamin E-blended UHMWPE exposed to 220°C. for 105 minutes, then extracted using a Tween 20 solution followed byfurther exposure to 220° C. was lower in the surface and in the bulkcompared to 1 wt % vitamin E blended UHMWPE exposed to 220° C. alone for105 minutes. Thus, the vitamin E concentration of vitamin E blendedUHMWPEs could be manipulated by multiple high temperature exposure andsurfactant solution extraction steps.

Example 18. Manipulation of Vitamin E Profile by Oven Extraction on OvenExtracted and Ethanol Treated Samples

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 1 wt % vitamin E concentration.

A puck (diameter 10 cm, thickness 1-1.1 cm) of 1 wt % vitaminE-containing UHMWPE blend was prepared via compression molding. Thepowder was pre-heated in a vacuum oven under partial vacuum/inert gas at190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press where it was sintered, then compressedto 20 MPa at about 194° C. for 10 minutes, then cooled to roomtemperature under pressure. Then, the puck was cooled for approximately1.5 hours under pressure.

Two cubes (10×10×10 mm) were machined from the puck and kept in a vacuumoven at a pressure of 2×10⁻⁶ atm and a temperature of 220° C. for 105minutes. Thereafter, samples were taken out of the oven and cooled inair at room temperature. One of the cubes was boiled in ethanol for 3hours and cooled in air. Thereafter, this cube was kept in a vacuum ovenat 2×10⁻⁶ atm pressure (argon) and a temperature of 220° C. for 60minutes. FTIR analysis was conducted on 150 micron sections obtainedfrom the center of both the cubes which were parallel to the bottom ofsurface of the oven (FIG. 7). Results are compared for both the samplesin FIG. 21. The vitamin E concentration profile of 1 wt % vitaminE-blended UHMWPE exposed to 220° C. for 105 minutes, then to boilingethanol for 3 hours, then to 220° C. for 60 minutes showed a decreasedsurface concentration of vitamin E. Therefore, these results showed thatthe vitamin E profile could be modified via performing multiple steps ofhigh temperature exposure followed by solvent extraction by ethanol.

Example 19. Surface Extraction of Vitamin E from Vitamin E-ContainingSamples Along with the Diffusion of Vitamin E from the Back SurfaceTowards Load Bearing Surface in a Nitrogen Convection Oven

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E, thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 3 wt % and 0.3 wt % vitamin E.

Two pucks (diameter 10 cm, thickness 1-1.1 cm) of 3 wt % and 0.3 wt %vitamin E-containing UHMWPE blend were prepared via compression molding.The powder was pre-heated in a vacuum oven under partial vacuum/inertgas at 190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press where it was sintered, then compressedto 20 MPa at about 194° C. for 10 minutes, then cooled to roomtemperature under pressure. Then, the puck was cooled for approximately1.5 hours under pressure.

Two cubes (10×10×10 mm) each were machined from these pucks and thelower concentration cube (0.3 wt % vitamin E cube) was placed on thehigher concentration cube (0.3 wt % vitamin E cube) before masking 5 ofthe six sides with aluminum foil. One circular surface with a lowerconcentration (0.3 wt % vitamin E cube) was left unmasked. The sampleswere placed in a pre-heated nitrogen convection oven at 290° C. with theunmasked surface exposed to nitrogen flow. The pucks were kept in theoven under these conditions for approximately 120 minutes. Samples wereremoved from the oven and were cooled in air to about room temperature.FTIR analysis was conducted on the 150 micron sections that wereobtained away from the edges (FIG. 1). Results are plotted as a functionof depth in FIG. 22. Here x=0 represents surface of the top puck whichinitially had 0.3 wt % of vitamin E while x=20 mm represents the bottomsurface which was masked and in contact with the bottom surface of theoven (FIG. 23). These results showed that simultaneous diffusion ofsample from the backside surface and extraction from the surface was aviable alternative to manufacture polymeric material with low vitamin Econcentration in the surface and high vitamin E concentration in thebulk.

Example 20. Radiation Cross-Linking of Surface Extracted and BulkDiffused Vitamin E Containing UHMWPE Pucks

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 3 wt % and 0.3 wt % vitamin E.

Two pucks (diameter 10 cm, thickness 1-1.1 cm) of 3 wt % and 0.3 wt %vitamin E-containing UHMWPE blend were prepared via compression molding.The powder was pre-heated in a vacuum oven under partial vacuum/inertgas at 190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press where it was sintered, then compressedto 20 MPa at about 194° C. for 10 minutes, then cooled to roomtemperature under pressure. Then, the puck was cooled for approximately1.5 hours under pressure.

Two pucks (10 cm diameter, 10 mm thick) were placed on top of each other(to extract from the top puck and diffuse vitamin E from the bottom pucktowards the surface of the top puck) and masked with aluminum foil onfive sides except for the top surface (0.3 wt % vitamin E puck). Sampleswere placed in a pre-heated nitrogen convection oven at 290° C. with theunmasked surface exposed to nitrogen flow. The pucks were kept in theoven under these conditions for approximately 290 minutes. Samples wereremoved from the oven and were cooled in air to about room temperature.After cooling, the top puck was irradiated by electron beam irradiationusing a Van-de-Graff generator at 3.0 MeV to a dose of 175 kGy at 25kGy/pass. FTIR analysis was conducted on the irradiated samples asdescribed in FIG. 1. The vitamin E index as a function of depth iscompared before and after irradiation in FIG. 24. The vitamin E indexwas decreased after irradiation and the vitamin E index at x=2 mm wasbelow the detection limit designated as a vitamin E index of 0.02.

The cross-link density of sections from the irradiated pucks wascalculated. Samples (3×3×1 mm) were cut by razor blade as shown in FIG.4. The samples were swollen in xylene pre-heated to 130° C. for 2 hours.Weights of sample were measured before and after xylene swelling.

Cross-link density was calculated using Equation 2.

The volumetric equilibrium expansion ratio, q_(eq), was calculated fromthe weight swelling ratio using a density for dry polyethylene of 0.94 gcm⁻³ and a density for xylene of 0.75 g cm⁻³ at 130° C. Cross-linkdensity is plotted as a function of depth in FIG. 25. The control was a0.3 wt % vitamin E blended UHMWPE puck (diameter 10 cm, thickness 1.1cm) prepared as described above and irradiated to 175 kGy. Cross-linkdensity of extracted and doped sample was higher than the control puckat the surface (p<0.01) while it was lower in bulk compared to samecontrol (p<0.01)

Example 21. Wear Rate of Surface Extracted and Bulk Diffused Vitamin EContaining UHMWPE Pucks

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin, thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 3 wt % and 0.3 wt % vitamin E respectively.

Two pucks (diameter 10 cm, thickness 1-1.1 cm) of 3 wt % and 0.3 wt %vitamin E-containing UHMWPE blend were prepared via compression molding.The powder was pre-heated in a vacuum oven under partial vacuum/inertgas at 190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press where it was sintered, then compressedto 20 MPa at about 194° C. for 10 minutes, then cooled to roomtemperature under pressure. Then, the puck was cooled in approximately1.5 hours under pressure.

Two pucks were placed on top of each other (to extract from the top puckand diffuse vitamin E from the bottom puck) and masked with aluminumfoil on 5 sides except one circular surface with the lower concentration(0.3 wt % vitamin E puck). Samples were placed in a pre-heated nitrogenconvection oven at 290° C. with the unmasked surface exposed to nitrogenflow. The pucks were kept in the oven under these conditions forapproximately 290 minutes. Samples were removed from the oven and werecooled in air at room temperature. After cooling, the top puck wasirradiated by electron beam irradiation using a Van-de-Graff generatorat 3.0 MeV to a dose of 175 kGy at 25 kGy/pass.

As specified earlier, cylindrical pins of 9 mm diameter and 9 mm lengthwere machined from the top 10 mm of the material by machining off 1 mmfrom the exposed surface and bi-directional pin-on-disk wear test wasconducted for the irradiated materials. Wear testing was conducted forapproximately 1 million cycles. Pins were tested against CoCr in bovineserum at 2 Hz. Weight loss was measured approximately every 0.125 MC andwear rate is reported as a linear regression of weight loss versusnumber of cycles from 0.5 MC to 1 MC. Wear rate for extracted andirradiated materials was 1.6±0.3 mg/MC and was statistically similar tothe wear rate of 0.1 wt % vitamin E blended material irradiated to 100kGy (1.1±0.2 mg/MC, p=0.13). These results are indicative that a highlywear resistant UHMWPE can be achieved by high temperature exposure forextraction of vitamin E from the surface with simultaneous doping fromvitamin E-blended UHMWPE followed by irradiation.

Example 22. Surface Extraction Accompanied by Diffusion of Vitamin Efrom the Posterior Surface Through Doped Porous Ceramic

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E, thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 0.3 wt % vitamin E concentration.

A puck (diameter 10 cm, thickness 1-1.1 cm) of 0.3 wt % vitaminE-containing UHMWPE blend was prepared via compression molding. Thepowder was pre-heated in a vacuum oven under partial vacuum/inert gas at190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press where it was sintered, then compressedto 20 MPa at about 194° C. for 10 minutes, then cooled to roomtemperature under pressure. Then, the puck was cooled in approximately1.5 hours under pressure.

Two cuboids (20×10×10 mm) were machined out of these pucks. Separately,two pieces of porous ceramic (Fisher, Pittsburgh, Pa.) were machined inform of small cylinders of 1 cm diameter and 1 cm as thickness.Thereafter, they were doped in pure vitamin E overnight for around 14hours. Each cuboid was placed on one porous ceramic cylinder such thatone 10×10 mm surface of the cuboid was in contact with ceramic. Thewhole assembly is masked with aluminum foil such that only one 10×10 mmsurface (surface opposite to the one in contact with ceramic) was leftexposed. Samples were kept in a nitrogen convection oven at 290° C. foreither 120 minutes or 210 minutes. After the designated time, sampleswere taken out of the oven and cooled in air at room temperature untilsteady state was reached. FTIR analysis was conducted on 150 micronsections obtained from the center of the cuboids such that x=0represents the surface exposed to nitrogen while x=20 is the surface incontact with the ceramic, similar to the method described in FIG. 1. Asshown in FIG. 26, the surface had very low concentrations of vitamin Eas compared to the bulk for both durations.

Example 23. Surface Extraction Along with Diffusion of Vitamin E fromthe Dip Coated Back Surface

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E, thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 0.3 wt % vitamin E concentration.

A puck (diameter 10 cm, thickness 1-1.1 cm) of 0.3 wt % vitaminE-containing UHMWPE blend was prepared via compression molding. Thepowder was pre-heated in a vacuum oven under partial vacuum/inert gas at190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press where it was sintered, then compressedto 20 MPa at about 194° C. for 10 minutes, then cooled to roomtemperature under pressure. Then, the puck was cooled for approximately1.5 hours under pressure.

A cube (10×10×10 mm) was machined out of the puck and dipped in vitaminE on 5 sides. The process of dip coating is better controlled using adip coater which aids in controlling the speed of dipping, therebyproviding a uniform film thickness on the sample. The 5 coated sideswere masked with aluminum foil and the sample was kept in a nitrogenconvection oven with the unexposed (non-coated) surface in contact withnitrogen. The oven was maintained at 290° C. and the sample was heatedfor 30 min. Thereafter, the sample was removed and cooled in air at roomtemperature until steady state was reached. FTIR analysis was conductedon 150 micron sections obtained from the center of the cubes where x=0represents the surface exposed to nitrogen and x=10 is the bottomsurface that was dip coated, masked with aluminum foil and in contactwith the bottom surface of the oven (FIG. 1). As depicted in FIG. 27,the surface had very low concentrations of vitamin E as compared to thebulk; therefore dip coating along with surface extraction by hightemperature exposure is a viable alternative to obtain lower surfaceconcentration of vitamin E on the samples as compared to the bulk.

Example 24. Manipulation of Vitamin E Profile in Surface Extracted andBack Side Vitamin E Doped Samples by Changing Time

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin, thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 3 wt % and 0.3 wt % vitamin E respectively.

Two pucks (diameter 10 cm, thickness 1-1.1 cm) of 3 wt % and 0.3 wt %vitamin E-containing UHMWPE blend were prepared via compression molding.The powder was pre-heated in a vacuum oven under partial vacuum/inertgas at 190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press where it was sintered, then compressedto 20 MPa at about 194° C. for 10 minutes, then cooled to roomtemperature under pressure. Then, the puck was cooled in approximately1.5 hours under pressure.

Two cubes (10×10×10 mm) each were machined from these pucks and thelower concentration cube was placed on the higher concentration cubebefore masking with aluminum foil on 5 sides of the sample. One circularsurface with the lower concentration (0.3 wt % vitamin E cube) was leftunmasked. They were placed in a pre-heated nitrogen convection oven at290° C. with the unmasked surface exposed to nitrogen flow. One set ofcubes was treated in the oven for 120 minutes while other set wastreated for 180 minutes. Samples were removed from the oven and werecooled in air at room temperature. FTIR analysis was conducted on 150micron sections obtained away from the edges (FIG. 1). Results areplotted as a function of depth in FIG. 28. Here x=0 represents thesurface of the top puck which initially had 0.3 wt % of vitamin Econcentration while x=20 mm represents the bottom surface which ismasked and in contact with the bottom surface of the oven. Data ispresented for the first 10 mm depth of the sample. As high temperatureexposure increased from 120 minutes to 180 minutes, the diffusion amountfrom the back side increased leading to an increase in vitamin Econcentration in the sample.

Example 25. Manipulation of Vitamin E Profile in Surface Extracted andBack Side Vitamin E Doped Samples by Changing Initial Concentration ofVitamin E in Samples Before Extraction

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 2 wt % and 0.3 wt % vitamin E.

Two pucks (diameter 10 cm, thickness 1-1.1 cm) of 3 wt % and 0.3 wt %vitamin E-containing UHMWPE blend were prepared via compression molding.Virgin (0% vitamin E) pucks were prepared by similar procedure, withoutmixing the vitamin E mixture with the UHMWPE powder. The powder waspre-heated in a vacuum oven under partial vacuum/inert gas at 190-210°C. for approximately 2 hours. Then, the mold/powder was transferred toan automatic press where it was sintered, then compressed to 20 MPa atabout 194° C. for 10 minutes, then cooled to room temperature underpressure. Then, the puck was cooled for approximately 1.5 hours underpressure.

Two cubes (10×10×10 mm) of concentration 0.3% and 3% were placed on topof each other (to extract from the top puck and diffuse vitamin E fromthe bottom puck towards the surface of the top puck) and masked withaluminum foil on 5 sides except for the top surface (0.3 wt % vitamin Epuck). An additional sample was prepared by placing a virgin cube(10×10×10 mm) on top of 3% vitamin E concentration cube (10×10×10 mm)and masking the 5 sides except the extraction surface (virgin puck).These two samples were placed in a pre-heated nitrogen convection ovenat 290° C. with the unmasked surface exposed to nitrogen flow. The cubeswere kept in the oven under these conditions for approximately 180minutes. Samples were removed from the oven and were cooled in air toabout room temperature. FTIR analysis was conducted on these samples asdescribed in FIG. 1. The vitamin E index as a function of depth iscompared for both the samples in FIG. 29. The samples with an initialconcentration of 0.3% in the top cube had surface concentrations greaterthan the samples with a virgin cube as the top cube.

Example 26. Manipulation of Vitamin E Profile in Surface Extracted andBack Side Vitamin E Doped Samples by Changing Initial Concentration ofVitamin E in Doping Medium

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 0.3 wt %, 2 wt %, and 3 wt % vitamin E.

Four pucks (diameter 10 cm, thickness 1-1.1 cm) of 5 wt %, 3 wt %, 2 wt% and 0.3 wt % vitamin E-containing UHMWPE blend were prepared viacompression molding. The powder was pre-heated in a vacuum oven underpartial vacuum/inert gas at 190-210° C. for approximately 2 hours. Then,the mold/powder was transferred to an automatic press where it wassintered, then compressed to 20 MPa at about 194° C. for 10 minutes,then cooled to room temperature under pressure. Then, the puck wascooled in approximately 1.5 hours under pressure.

Two cubes (10×10×10 mm) of concentration 0.3% and 2% were placed on topof each other (to extract from the top puck and diffuse vitamin E fromthe bottom puck towards the surface of the top puck) and masked withaluminum foil on 5 sides except for the top surface (0.3 wt % vitamin Epuck). Another sample was prepared by placing 0.3 wt % (10×10×10 mm) ontop of 3% vitamin E concentration cube (10×10×10 mm) and masking the 5sides except the extraction surface (virgin puck). A third sample wasprepared in a similar way except that a 5 wt % cube was used as thebottom cube. These three samples were placed in a pre-heated nitrogenconvection oven at 290° C. with the unmasked surface exposed to nitrogenflow. The cubes were kept in the oven under these conditions forapproximately 180 minutes. Samples were removed from the oven and werecooled in air to about room temperature. FTIR analysis was conducted onthese samples as described in FIG. 1. The vitamin E index as a functionof depth is compared for both the samples in FIG. 30. As theconcentration of vitamin E in the bottom cube (doping medium) wasincreased, the bulk concentration increased in the top puck, while thesurface concentration remained similar for each of the samples.

Example 27. Manipulation of Vitamin E Profile in Surface Extracted andBack Side Vitamin E Doped Samples by Changing Number of Layers Used as aDoping Medium

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 0.3 wt % and 2 wt % vitamin E.

Three pucks (diameter 10 cm, thickness 1-1.1 cm) of 5 wt %, 2 wt % and0.3 wt % vitamin E-containing UHMWPE blend were prepared via compressionmolding. The powder was pre-heated in a vacuum oven under partialvacuum/inert gas at 190-210° C. for approximately 2 hours. Then, themold/powder was transferred to an automatic press where it was sintered,then compressed to 20 MPa at about 194° C. for 10 minutes, then cooledto room temperature under pressure. Then, the puck was cooled inapproximately 1.5 hours under pressure.

Two cubes (10×10×10 mm) of concentration 0.3% and 5% were placed on topof each other (to extract from the top puck and diffuse vitamin E fromthe bottom puck towards the surface of the top puck) and masked withaluminum foil on 5 sides except for the top surface (0.3 wt % vitamin Epuck). Another sample was prepared by placing 0.3 wt % (10×10×10 mm) ontop of 2% vitamin E concentration cuboid of 2 mm depth (10×10×2 mm)followed by a cube (10×10×10 mm) of 5 wt % vitamin E concentration andthen masking the 5 sides except for the extraction surface (0.3 wt %cube). A third sample was prepared in a manned analogous to thepreparation of the second sample, with three layers from top to bottomhaving the concentration of 0.3 wt %, 2 wt % and 5 wt % respectively.These three samples were placed in a pre-heated nitrogen convection ovenat 290° C. with the unmasked surface exposed to nitrogen flow. First twosamples were kept in the oven under these conditions for approximately120 minutes. The third sample was kept in oven with nitrogen flow at290° C. for 180 minutes. Samples were removed from the oven and werecooled in air to about room temperature. FTIR analysis was conducted onthese samples as described in FIG. 1. The vitamin E index as a functionof depth was compared for both the samples in FIG. 31. After anadditional 2 mm layer of 2 wt % vitamin E is sandwiched between 2 layers(sample 2 and sample 3), the surface concentration of top cube (0.3 wt %vitamin E) after extraction is same as sample 1 (with two layers) whilethe bulk concentration is lower than the sample with just two layers(sample 1).

Example 28. Manipulation of Vitamin E Profile in Surface Extracted andBack Side Vitamin E Doped Samples by Changing the Masking Type or notMasking the Back Surface

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 0.3 wt % vitamin E concentration.

Two pucks (diameter 10 cm, thickness 1-1.1 cm) of 5 wt % and 0.3 wt %vitamin E-containing UHMWPE blend were prepared via compression molding.The powder was pre-heated in a vacuum oven under partial vacuum/inertgas at 190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press where it was sintered, then compressedto 20 MPa at about 194° C. for 10 minutes, then cooled to roomtemperature under pressure. Then, the puck was cooled in approximately1.5 hours under pressure.

A cube (10×10×10 mm) of concentration 0.3 wt % vitamin E was placed on acuboid of 4 mm thickness (10×10×4 mm) and 5 wt % initial vitamin Econcentration (to extract from the top cube and diffuse vitamin E fromthe bottom cuboid towards the surface of the top cube) and stacked cubeswere masked with aluminum foil on four sides excluding the top surface(0.3 wt % vitamin E) and bottom surface (5 wt % vitamin E). Threesamples were prepared in a similar way and were placed in a pre-heatednitrogen convection oven at 290° C. with the top and bottom surfaceexposed to nitrogen flow. Samples remained in the oven for 150 minutes,160 minutes and 180 minutes, respectively. Samples were then removedfrom the oven and were cooled in air to about room temperature. FTIRanalysis was conducted on these samples as described in FIG. 1, with x=0being the surface of the exposed top or low concentration cube (0.3 wt %vitamin E). The vitamin E index as a function of depth is compared forall the three samples in FIG. 32. As the duration of heating in the ovenwas increased from 150 minutes to 180 minutes, both, the measuredsurface and bulk concentrations decreased.

Example 29. Tensile Testing of Surface Extracted and RadiationCross-Linked Vitamin E Containing UHMWPE Pucks

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin E, thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 1 wt % vitamin E.

Two pucks (diameter 10 cm, thickness 1-1.1 cm) of the 1 wt % vitaminE-containing UHMWPE blend were prepared via compression molding. Thepowder was pre-heated in a vacuum oven under partial vacuum/inert gas at190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press (3895 Auto-M, Carver, Wabash, Ind.)where it was sintered, then compressed to 20 MPa at about 194° C. for 10minutes, then cooled to room temperature under pressure. Then, the puckwas cooled for approximately 1.5 hours under pressure.

Two pucks were placed on top of each other (to obtain a sample withdouble the effective diffusion distance from the surface) and maskedwith aluminum foil on 5 sides except for one circular surface. Thesamples were placed in a pre-heated nitrogen convection oven at 290° C.with the unmasked surface exposed to nitrogen flow. The pucks were keptin the oven under these conditions for approximately 290 min. Sampleswere removed from the oven and were cooled in air at room temperature.

Following the cooling step, the top puck was irradiated by electron beamirradiation using a Van-de-Graff generator at 3.0 MeV to a dose of 175kGy at 25 kGy/pass. One thin section each (3.2 mm thick) was machinedclose to the top or bottom of the extracted and irradiated puck.Dog-bones were stamped from these thin sections and tested at 10 mm/minin tension according to ASTM D-638 (Type V; n=4). Yield strength (YS),ultimate tensile strength (UTS) and elongation to break (EAB) arereported. Elongation to break was determined by a laser extensometer.The results are reported in Table 1 below.

TABLE 1 The tensile mechanical properties of high temperature extractedand radiation cross-linked 1 wt % vitamin E-blended UHMWPE Yield StressBreak Stress Elongation at break (MPa) (MPa) (%) Extracted, irradiated21 ± 2 31 ± 4 226 ± 12 surface Extracted, irradiated 22 ± 1 41 ± 3 327 ±26 bulk

There was no difference in the yield strength (YS) of the surface andbulk regions of extracted and irradiated UHMWPE (Table 1). The bulkregion of the extracted and irradiated UHMWPE had higher UTS and EABthan that of the surface (p<0.01 and p<0.01, respectively).

TABLE 2 The tensile mechanical properties of high temperatureextracted-doped and radiation cross-linked 0.3 wt % vitamin E-blendedUHMWPE Yield Stress Break Stress Elongation at break (MPa) (MPa) (%)Extracted, irradiated 21 ± 0.1 37 ± 5 228 ± 11 surface Extracted,irradiated 22 ± 0.3 45 ± 8 361 ± 29 bulk

Example 30 Tensile Testing of Surface Extracted, Bulk Diffused andRadiation Cross-Linked Vitamin E Containing UHMWPE Pucks

A 5 wt % concentration mixture of vitamin E with UHMWPE (GUR 1050) wasprepared by first mixing isopropyl alcohol (IPA) with vitamin, thenmixing the vitamin E-IPA solution with virgin UHMWPE powder, thenevaporating off the solvent in a vacuum oven at an elevated temperature(approximately 60° C.). The mixture was diluted with GUR 1050 to obtainGUR 1050 with 3 wt % and 0.3 wt % vitamin E respectively.

Two pucks (diameter 10 cm, thickness 1-1.1 cm) of 3 wt % and 0.3 wt %vitamin E-containing UHMWPE blend were prepared via compression molding.The powder was pre-heated in a vacuum oven under partial vacuum/inertgas at 190-210° C. for approximately 2 hours. Then, the mold/powder wastransferred to an automatic press where it was sintered, then compressedto 20 MPa at about 194° C. for 10 minutes, then cooled to roomtemperature under pressure. Then, the puck was cooled for approximately1.5 hours under pressure.

Two pucks were placed on top of each other (to extract from the top puckand diffuse vitamin E from the bottom puck) and masked with aluminumfoil from 5 sides except one circular surface with lower concentration(0.3 wt % vitamin E puck). They were placed in a pre-heated nitrogenconvection oven at 290° C. with the unmasked surface exposed to nitrogenflow. The pucks were kept in the oven under these conditions forapproximately 290 minutes. Samples were removed from the oven and werecooled in air at room temperature. After cooling down, the top puck wasirradiated by electron beam irradiation using a Van-de-Graff generatorat 3.0 MeV to a dose of 175 kGy at 25 kGy/pass.

Thin sections (2 mm thick) were cut from the surface (1-3 mm) and bulk(7-9 mm) regions of the top puck and dog bones were stamped for tensilemeasurements. Testing was performed according to ASTM D-638 method at acrosshead displacement of 10 mm/min (Type 5; n=4). Yield strength (YS),ultimate tensile strength (UTS) & elongation to break (EAB) arereported. Strain was measured by a laser extensometer. Beforeirradiation, there was no significant difference between the mechanicalstrength (UTS) of the top section (surface) and bottom section (bulk)obtained from the top puck. While after irradiation, the materialstrength of the top section (UTS) decreased from 45.7±3.1 MPa to36.7±4.8 MPa (p=0.03) with bulk strength still the same as itsnon-irradiated counterpart (Table 2).

Although the present invention has been described in detail withreference to certain embodiments, one skilled in the art will appreciatethat the present invention can be practiced by other than the describedembodiments, which have been presented for purposes of illustration andnot of limitation. Therefore, the scope of the invention should not belimited to the description of the embodiments contained herein.

All documents cited herein are, in relevant part, incorporated herein byreference; the citation of any document is not to be construed as anadmission that it is prior art with respect to the present invention.

What is claimed is:
 1. A method of making an additive-doped polymericmaterial, the method comprising: (a) doping a consolidated polymericmaterial with at least one additive by diffusion to form a consolidatedadditive-doped polymeric material; (b) heating at least a portion of atleast one surface of the additive-doped polymeric material to form aheated consolidated additive-doped polymeric material; and (c) coolingthe heated consolidated additive-doped polymeric material to form acooled consolidated additive-doped polymeric material, thereby forming apolymeric material with a spatially controlled distribution of additive.2. The method of claim 1, wherein step (a) further comprisesconsolidating a polymeric material to form the consolidated polymericmaterial before doping the consolidated polymeric material.
 3. Themethod of claim 2, wherein the polymeric material is selected from anextrudate, pellets, a resin powder, flakes, a liquid, or a gel.
 4. Themethod of claim 2, wherein consolidating the polymeric materialcomprises at least one of compression molding, ram extrusion, extrusion,hot or cold isostatic pressing, injection molding, and directcompression molding.
 5. The method of claim 2, wherein step (a) furthercomprises blending the polymeric material with at least one additionaladditive before consolidating the polymeric material.
 6. The method ofclaim 5, wherein the at least one additional additive is selected froman antioxidant, vitamin E, and an anti-cross-linking agent.
 7. Themethod of claim 1, wherein step (a) further comprises consolidating apolymeric material to form the consolidated polymeric material andmachining the consolidated polymeric material before doping theconsolidated polymeric material.
 8. The method of claim 1, wherein step(c) further comprises irradiating the cooled consolidated additive-dopedpolymeric material.
 9. The method of claim 8, wherein step (c) furthercomprises annealing the cooled consolidated additive-doped polymericmaterial after it has been irradiated.
 10. The method of claim 1,wherein step (c) further comprises machining the cooled consolidatedadditive-doped polymeric material.
 11. The method of claim 1, whereinstep (c) further comprises machining the cooled consolidatedadditive-doped polymeric material and thereafter irradiating the cooledconsolidated additive-doped polymeric material.
 12. The method of claim1, wherein steps (a) and (b) are concurrent.
 13. The method of claim 1,wherein the at least one additive is selected from an antioxidant,vitamin E, and an anti-cross-linking agent.
 14. The method of claim 1,wherein step (b) further comprises masking at least one of the surfacesof the material before heating at least a portion of at least onesurface of the consolidated additive-doped polymeric material, therebypreventing extraction.
 15. The method of claim 14, wherein step (b)further comprises using a masking material for masking at least one ofthe surfaces of the material, the masking material being a metal. 16.The method of claim 1, wherein step (b) further comprises heating in thepresence of at least one of an inert gas, a non-inert gas, air, avacuum, a liquid, a liquid with gas bubbled through, a liquid saturatedwith gas, a supercritical fluid, a convection current, and combinationsthereof.
 17. The method of claim 1, wherein step (a) further comprisesusing a doping source for doping the consolidated polymeric material,the doping source being selected from blended polyethylene with at leastone antioxidant, polyethylene doped with at least one antioxidant viadiffusion, at least one free antioxidant, porous ceramic doped with atleast one antioxidant via diffusion, porous polyethylene doped with atleast one antioxidant via diffusion, and porous polytetrafluoroethylenedoped with at least one antioxidant via diffusion.
 18. The method ofclaim 1, wherein step (b) further comprises extracting the polymericmaterial from the consolidated additive-doped polymeric material priorto heating the consolidated additive-doped polymeric material.
 19. Themethod of claim 1, wherein step (b) further comprises extracting thepolymeric material from the heated consolidated additive-doped polymericmaterial.
 20. The method of claim 18, wherein the step of extractingcomprises at least one of a liquid, gas and fluid extraction.